Keywords: Gene drive synthetic
CRISPR-Cas9 suppression gene drives for Nile tilapia control: prospects in sub-Saharan African freshwater ecosystems
35509Bobo, E. D., All Life, 19. 2026-03-16 15:14:01.
CRISPR-based suppression gene drives represent a promising tool for managing invasive Nile tilapia (Oreochromis niloticus) populations in sub-Saharan Africa’s freshwater ecosystems. Introduced through aquaculture, Nile tilapia supports livelihoods but also causes severe biodiversity loss. This review explores the technical feasibility of CRISPR-Cas9 suppression gene drives, specifically homing and Driving-Y drive systems, as species-specific, potentially self-sustaining biocontrol strategies. The theoretical effectiveness of these gene drive systems in reducing invasive Nile tilapia and restoring ecological balance is discussed within a precautionary framework. This study addresses the urgent need to protect native tilapia species, which are listed as Critically Endangered, Endangered, and Vulnerable by the IUCN. Gene drives have the potential to reduce invasive populations and restore ecological balance. However, their effectiveness can be compromised by extensive hybridization with native Oreochromis species and resistance evolution in genetically diverse populations. Therefore, the ecological, ethical, and socioeconomic risks of gene drive systems were examined in the context of the Convention on Biological Diversity and Cartagena Protocol. Hence, integrating molecular innovations with strong policy frameworks, stakeholder engagement, and comprehensive risk assessment is essential. CRISPR-Cas9 suppression drives deployment requires careful evaluation across ecological, ethical, and governance contexts to safeguard native ichthyofauna.
Editorial Overview – Insect Genomics (2026): enhancing public health, food security, and biodiversity through genetic biocontrol.
35506Yoosook Lee, Omar S. Akbari, Current Opinion in Insect Science, 2026-03-13 09:43:24.
Genetic biocontrol is a form of biological control in which genetic variants or genetically modified forms of the target species act to reduce or eliminate the target species. In entomology, target species include agricultural pests and vector species that transmit pathogens to human, animal, or plant systems. Examples include the Anopheles mosquito gene drive system to reduce or replace malaria vectors in Africa, the use of Wolbachia symbiont induced cytoplasmic incompatibility in Culex mosquitoes to project Hawaiian native birds from avian malaria related deaths, and the use of CRISPR to generate sterile males at a scale useful for suppressing pests of fruit crops. The widespread availability of robust transgenic technologies combined with new RNA-guided DNA endonuclease-based genome manipulation technologies and platforms and advances in synthetic biology are fueling the development of genetic biocontrol technologies and systems for combating arthropods that contribute to food insecurity, pathogen- and parasite-transmission, and invasive arthropods that threaten biodiversity. Heretofore a niche area of genetic biocontrol now commands great interest and an ever-growing number of applications.
Liverpool School of Tropical Medicine joins the Target Malaria Consortium
35499Dr. Tony Nolan, Target Malaria: News, 2026-03-10 09:34:21.
Target Malaria has so far been working on the three widespread vectors of the Anopheles gambiae species complex: An. coluzzii, An. gambiae, and An. arabiensis. As members of a species complex, these three species are morphologically indistinguishable. Together, they are among the most important malaria vectors in sub-Saharan Africa. Although they are distinct species, they can occasionally inter-breed. In addition, Anopheles funestus is a widespread vector across sub-Saharan Africa. It is more distantly related to the gambiae species complex and is not capable of hybridising with those species. An. funestus has distinct ecological characteristics and is a highly efficient vector of malaria – its species name, funestus, means “deadly”. In some areas, it is the dominant contributor to malaria transmission. Modelling indicates that achieving the full public health impact of gene drive will require trageting of An. funestus, as malaria transmission in many regions is shared between multiple vector species. Anopheles funestus is particularly challenging to colonise and maintain in the laboratory. Our team at the Liverpool School of Tropical Medicine was among the first to demonstrate stable genetic modification of An. funestus, establishing the technical foundation required to explore gene drive approaches in this species. Through joining Target Malaria, we will extend gene drive research beyond the gambiae complex and support the development of multi-species gene drive strategies for malaria control.
Potential benefits, opportunities, risks and challenges of population suppression gene drive mosquitoes for malaria control described in the scholarly literature: a rapid scoping review
35472Fürer, C. L., Fischer, T. B., Suter, T., Winkler, M. S., and Knoblauch, A. M., Impact Assessment and Project Appraisal, 2026-02-27 18:07:52.
Gene drive mosquitoes represent a promising strategy to alter mosquito populations and reduce disease transmission. However, their use has generated considerable debate due to ecological, ethical, and societal concerns. This paper reviews risks, challenges, benefits, and opportunities of gene drive technology, focusing on environmental, social, economic, and health implications. A literature search of peer-reviewed articles published between January 2019 and September 2023 was conducted using PubMed, Cochrane, Embase (Elsevier), and Google Scholar. Eligible papers included keywords such as ‘gene drive’, ‘mosquitoes’, and ‘Anopheles’. Extracted statements were grouped as ‘risks/challenges’, ‘benefits/opportunities’, or ‘ambivalent’, and classified across five dimensions: environmental/entomological/ecological, social, economic, health, and technological. From 1304 papers identified, 53 were included, yielding 892 statements. Of these, 66.5% addressed ‘risks/challenges’, 26.3% ‘benefits/opportunities’, and 7.2% were ‘ambivalent’. Most statements were classified under the ‘environmental/entomological/ecological’ dimension (46.1%), followed by ‘social’ (24.6%), ‘health’ (18.5%), ‘GM technology’ (7.2%), and ‘economic’ (3.6%). Commonly cited ‘risks/challenges’ included potential off-target effects, fitness costs, and development of resistance. The breadth of identified considerations, alongside the predominantly risk-focused discourse, highlights the need for multidimensional assessments. Early evaluations should integrate biosafety assessments with inclusive frameworks such as Strategic Environmental Assessments (SEA) and Environmental, Social, and Health Impact Assessments (ESHIA) to support responsible deployment.
Advances in CRISPR gene drives for mosquito population control
35449Robyn Raban, Anthony A James, Omar S Akbari, Current Opinion in Microbiology, 90. 2026-02-12 19:25:19.
CRISPR-based gene drive (GD) systems bias allele inheritance during meiosis, enabling transgenes to spread at rates exceeding Mendel’s law of segregation. This capability underlies their potential as powerful tools for controlling mosquito-borne diseases. GDs can be engineered either to suppress mosquito populations or to modify them by introducing traits that block pathogen transmission. Recent advances have focused on improving evolutionary stability, with modeling studies providing insights into expected population dynamics. With a focus on the most current population modification GDs, we discuss advances in GD architectures — including integral and allelic drives, combined modification–suppression systems, and both homing and non-homing toxin–antidote designs — that expand the range of possible strategies and address limitations of early homing drives. Numerous antipathogen effectors with strong pathogen-blocking activity can now be coupled to these systems, with current efforts assessing their durability against genetically diverse pathogens. Key challenges remain, including resistance evolution, ecological impacts, and long-term stability. Nonetheless, GDs offer a promising approach for reducing disease transmission, especially in regions where conventional interventions are difficult to sustain.
Assessing target genes for homing suppression gene drive
35447Xu, X., Fang, J., Chen, J. et al., The EMBO Journal, 2026-02-06 17:52:26.
Gene drives are engineered alleles that bias their own inheritance in offspring, enabling the spread of specific traits throughout a population. Targeting female fertility genes in a gene drive can be an efficient strategy for population suppression. In this study, we investigated nine female fertility genes in Drosophila melanogaster using CRISPR-based homing gene drives. Employing a multiplexed gRNA approach to prevent the formation of functional resistance alleles, we aimed to maintain high drive-conversion efficiency with low fitness costs in female drive-carriers. Drive efficiency was assessed in individual crosses and had varied performance across different target genes. Notably, drives targeting the octopamine β2 receptor (oct) and stall (stl) genes exhibited the highest drive-conversion rates and were further tested in cages. A drive targeting stl successfully suppressed a cage population with a high release frequency, though suppression failed in another replicate cage with a lower initial release frequency. Fitness costs in female drive carriers were observed in test cages, impacting the overall efficiency of population suppression. Further tests on the fertility of these lines using individual crosses indicated that some fitness costs were due to maternal deposition of Cas9 combined with new gRNA expression, which would only occur in progeny of drive males when testing split drives with separate Cas9 (when mimicking cages with complete drives) but not for complete drive systems. This could enable success in complete drives with higher maternal Cas9 deposition, even if cage experiments in split drives fail. Overall, our findings identify oct and stl as promising fertility targets and demonstrate both the potential and the constraints of fertility-based suppression drives, providing empirical evidence to guide the design and assessment of more efficient population control strategies.
Mapping Gene Drive Dynamics onto Mendelian Models
35414Zihang Wen, Monica Wan, Gili Greenbaum, Oana Carja, bioRxiv, 2026-01-30 16:46:40.
CRISPR-based gene drives bias their own transmission and can spread even when deleterious, giving rise to evolutionary dynamics that can be substantially more complex than those governed by standard Mendelian inheritance. Identifying conditions under which gene-drive dynamics can be faithfully approximated by Mendelian models would therefore enable the extensive theoretical toolkit of classical population genetics to be applied to gene-drive systems. Here, we develop a general mapping framework that translates gene-drive models into dynamically equivalent Mendelian models, allowing their behavior to be analyzed using classical theory. By deriving both haploid and diploid effective-parameter mappings, we identify Mendelian models that closely reproduce allele-frequency trajectories of gene drives across a wide range of conversion rates, fitness costs, and dominance effects. We delineate the regions of the parameter space where a one-parameter haploid approximation provides an accurate first-order representation, and where incorporating dominance in a diploid mapping substantially improves fidelity and recovers internal equilibria and threshold behavior. Analytic approximations yield efficient mappings across most of the drive parameter space, while a trajectory-based grid search further improves accuracy near nonlinear regime boundaries. To demonstrate the utility of this framework, we apply it to predicting gene swamping in a two-deme migration-selection model and show that the mapped Mendelian system accurately forecasts transitions between fixation and loss under three relevant release scenarios: environmental variation in fitness, engineered fitness asymmetries, and environment-dependent conversion. Together, these results establish a theoretical bridge between non-Mendelian gene drives and classical population genetic models, providing an interpretable and computationally efficient foundation for predicting gene-drive outcomes and guiding the design of gene drive systems and deployment strategies.
Gene drives tested against real-world malaria diversity
35377Marchal, I, Nature Biotechnology, 44. 2026-01-16 16:30:43.
Gene drive technology, which uses genetic engineering to propagate selected genes throughout a population, is a potential strategy for blocking the spread of malaria, either by suppressing mosquito populations or by making them unable to transmit the disease. However, gene drive mosquitos have mainly been tested in laboratory settings with decade-old Plasmodium parasite strains, and it is unknown whether they can block the transmission of genetically diverse Plasmodium now in circulation. In an important step toward application, Habtewold et al. now report in Nature the adaptation of a previously developed gene drive strategy to an African context.
Increasing the effective gene drive homing rate by targeting the haploinsufficient spermatogenesis gene KLHL10
35323Ceili L. Peng, W. Sebastian Kamau, Julien Freeman, et al., bioRxiv, 2026-01-05 12:04:02.
CRISPR-based gene drives represent a powerful new technology for limiting disease transmission and controlling invasive populations. These systems rely on homology-directed repair (HDR) to ‘drive’ a genetic element through a population. However, mammals tend to favor non-homologous end joining (NHEJ), which generates mutations that halt further drive propagation. Here, we describe the experimental characterization of a gene drive system targeting the haploinsufficient spermatogenesis gene KLHL10 in the laboratory mouse. Using a newly designed ‘coding sequence cassette’ we introduce downstream guide RNAs within the gene, ensuring that sperm undergoing NHEJ are selectively removed from the population. As a proof of principle, we demonstrate that targeting KLHL10 with constitutively expressed LbCas12a results in strong selection against frameshift-containing sperm, validating the core purification mechanism required for this drive strategy. Unexpectedly, we also observed that female offspring lacked most frameshift mutations, suggesting a previously unrecognized role for KLHL10 in oogenesis or early embryonic development.
Genetic trick to make mosquitoes malaria resistant passes key test
35307Michael Le Page, New Scientist, 2025-12-10 17:06:06.
A genetic technology known as a gene drive could help prevent malaria by spreading genes in wild mosquitoes that stop them transmitting the parasite. Tests in a lab in Tanzania have now confirmed that one potential gene drive should achieve this if it were released in the country. “It would be a game-changing technology, that’s for sure,” says George Christophides at Imperial College London. A specific piece of DNA in the genome of an animal is normally passed on to only half its offspring, because a parent’s DNA is divided in half among egg or sperm. Gene drives increase this proportion, meaning a bit of DNA can spread rapidly through a population even if it provides no evolutionary benefit. There are many natural gene drives that work via all kinds of mechanisms – perhaps even in some human populations – and in 2013, biologists developed artificial gene drives using CRISPR gene-editing technology, which works by copying pieces of DNA from one chromosome to another. The idea is to use these drives to spread bits of DNA that block malaria transmission – but which bits? Christophides reported in 2022 that the development of malaria parasites inside mosquitoes can be greatly reduced by two tiny proteins, one derived from honeybees and the other from the African clawed frog.
Cattle Q&A with Brinda Dass, GeneConvene Global Collaborative
35243Tyrell Marchant, Progressive Cattle, 2025-10-15 08:41:35.
What factors have led to the northward spread of New World screwworm (NWS) over the past year after so many decades of successful eradication in Mexico and the U.S.? DASS: The northward spread of NWS after decades of eradication reflects a convergence of biological, environmental and programmatic factors. Climate change and increasing temperatures have created favorable conditions for pupal survival and year-round reproduction, enabling rapid reinvasion from subtropical regions. NWS biology – especially females’ ability to lay multiple waves of eggs in wounds – allows populations to surge quickly even from small footholds. High-density livestock practices and insufficient inspection of animal trade further accelerate spread, with smuggling through the Darién Gap undermining surveillance. Wildlife, pets and humans act as reservoirs, compounding detection challenges. Sterile insect technique (SIT), historically successful, has been overwhelmed: Production of sterile flies cannot match population growth, forcing control lines northward. Budget constraints, political disputes and reduced funding have further weakened monitoring and response systems. Together, these dynamics explain how a long-maintained eradication barrier collapsed, allowing NWS to expand northward at alarming speed.
The role of the transformer gene in sex determination and its employment in CRISPR/Cas9-based homing gene drive in the global fruit pest Drosophila suzukii
35185Dan Deng, Xueying Yi, Wen Wen, Liuqing He, Wei Peng, Insect Biochemistry and Molecular Biology, 184. 2025-09-29 08:45:13.
Sex determination of Diptera is established by the cascade genes such as transformer (tra), though the primary signals for sex determination differ among different insects. Here, we report the isolation, expression and function of tra gene in an invasive pest, Drosophila suzukii, and study the potential use of the D. suzukii tra (Dstra) gene in CRISPR/Cas9-based homing gene drive for genetic-based pest management. The Dstra gene is highly conserved in structure and has a sex-specific transcript. To test the function of this gene in sex determination, Dstra dsRNA was injected into embryos. Almost all XX embryos developed into masculinized phenotypic male adults with intersex morphology. Abnormal ovaries were revealed in XX pseudomales upon dissection. Based on the necessary role of Dstra for female development, we developed and evaluated a homing gene drive that targets Dstra in D. suzukii. The drive component consisting of multiplex Dstra single guide RNAs and Cas9 with Dsvasa promoter was introduced into the Dstra locus. Abnormal development of both the external genitalia and gonads was observed in G0 and G1 chromosomal female adults that expressed the male-specific doublesex (dsx) transcript. Interestingly, knocking out Dstra led to significantly reduced fertility in adults of corresponding sex and moderate transmission rates of the DsRed gene (63.54 %) were observed. Our results not only confirm the conserved function of the Dstra gene in sex determination, but also highlight the potential of sex conversion-based suppression gene-drive strategy targeting the Dstra gene in controlling of D. suzukii populations.
Natural Selection of Synthetic Gene Drives for Population Suppression Can Favor an Intermediate Strength of Drive
35141P. J. Beaghton and Austin Burt, The American Naturalist, 206. 2025-09-16 15:55:03.
Synthetic gene drives are being investigated as tools to suppress pest populations, and it is important to understand how natural selection will act on variant drivers that may either arise by de novo mutation or be intentionally released. In this study, we extend previous spatially implicit stochastic models to examine the evolutionary dynamics of synthetic driving Y chromosomes in patchy environments when population size is responding dynamically to the spread of the driver and derive conditions for the existence of an evolutionarily stable strategy (ESS) for drive strength. Under broad conditions, an intermediate drive strength emerges as the ESS, capable of outcompeting both stronger and weaker variants. Additionally, we show how the intentional release of two drivers straddling the ESS can help stabilize population dynamics. Finally, inbreeding depression has the effect of expanding the range of conditions under which no intermediate ESS exists, with ever stronger drive being selected until the population is eliminated. These results provide insights into the expected evolutionary trajectories of gene drive systems, with important implications for the design and release of gene drives for pest and vector control.
Synthetic Homing Endonuclease Gene Drives to Revolutionise Aedes aegypti Biocontrol – Game Changer or Pipe Dream?
34756Joshua X.D. Ang, Sebald A.N. Verkuijl, Michelle A.E. Anderson, Luke Alphey, Current Opinion in Insect Science, 2025-04-10 09:10:46.
The increasing burden of Aedes aegypti-borne diseases, particularly dengue, is a growing global concern, further exacerbated by climate change. Current control strategies have proven insufficient, necessitating novel approaches. Synthetic homing endonuclease gene (sHEG) drives represent one of the few emerging technologies with the potential to offer a cost-effective and equitable solution to this escalating public health challenge. However, despite multiple attempts, the homing efficiencies of Ae. aegypti sHEG systems lag behind those achieved in Anopheles mosquitoes. We discuss key insights from efforts to develop sHEGs in Ae. aegypti and highlight critical factors that may unlock further advances in this species.
Overcoming drug-resistant tumors with selection gene drives
31594Hui Wang, Mingqi Xie, Cell Genomics, 4. 2024-09-17 12:48:55.
Drug resistance is a major hurdle prohibiting effective treatment of many diseases, including cancer. Using model-guided designs, Leighow et al.1 engineered a dual-switch selection gene drive system custom designed to combat drug-resistant tumors. By demonstrating remarkable killing efficacies in preclinical models using human non-small lung cancer cells in vitro and in mice, this work describes an attractive mindset to develop next-generation anticancer therapies.
The haplolethal gene wupA of Drosophila exhibits potential as a target for an X-poisoning gene drive
28845Clancy D. Lawler, Ana Karla Parra Nuñez, Natalia Hernandes, Soumitra Bhide, Isabelle Lohrey, Simon Baxter, Charles Robin, bioRxiv, 2024-01-28 12:54:44.
A synthetic gene drive that targets haplolethal genes on the X-chromosome can skew the sex ratio towards males. Like an ‘X-shredder’ it does not involve ‘homing’ and that has advantages including the reduction of gene drive resistance allele formation. We examine this ‘X-poisoning’ strategy by targeting four of the 11 known X-linked haplolethal/haplosterile genes of Drosophila melanogaster with CRISPR/Cas9. We find that targeting the wupA gene during spermatogenesis skews the sex ratio so fewer than 14% of progeny are daughters. That is unless we cross the mutagenic males to X^XY female flies that bear attached-X chromosomes, which reverses the inheritance of the poisoned X chromosome so that sons inherit it from their father; in which case only 2% of the progeny are sons. These sex ratio biases suggests that most of the CRISPR/Cas9 mutants we induced in the wupA gene are haplolethal but some are recessive lethal. The males generating wupA mutants do not suffer from reduced fertility rather the haplolethal mutants arrest development in the late stages of embryogenesis well after fertilized eggs have been laid. This provides a distinct advantage over genetic manipulation strategies involving sterility which can be countered by the remating of females. We also find that wupA mutants that destroy the nuclear localization signal of shorter isoforms are not haplolethal as long as the open reading frame remains intact. Like D. melanogaster wupA orthologs of D. suzukii and Anopheles mosquitos are found on X chromosomes making wupA a viable X-poisoning target in multiple species.
Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata
28802Meccariello, A., Hou, S., Davydova, S. et al., Nature Communications, 15:372. 2024-01-15 17:13:20.
Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set of gene drives in a tephritid agricultural pest species, the Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that the medfly is highly amenable to homing-based gene drive strategies. By targeting the medfly transformer gene, we also demonstrate how CRISPR-Cas9 gene drive can be coupled to sex conversion, whereby genetic females are transformed into fertile and harmless XX males. Given this unique malleability of sex determination, we modelled gene drive interventions that couple sex conversion and female sterility and found that such approaches could be effective and tolerant of resistant allele selection in the target population. Our results open the door for developing gene drive strains for the population suppression of the medfly and related tephritid pests by co-targeting female reproduction and shifting the reproductive sex ratio towards males. They demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.
Transformative Novel Technologies and Global Environmental Governance
28377F. Rabitz, Cambridge University Press, 2023-11-13 09:55:21.
Transformative Novel Technologies are potential gamechangers for confronting climate change, biodiversity loss, and many other elements of the global environmental crisis, allowing us to achieve a more sustainable future. The contemporary and future international governance of these technologies has crucial implications for managing the global transition towards sustainability. This book is the first to present a comprehensive assessment of the impact of these technologies on international politics. The author examines the responses of international institutions to the emergence of these technologies, focusing on three broad domains: biotechnology, climate engineering, and mineral extraction in areas beyond national jurisdiction (the ocean floor or near-Earth asteroids). This book is aimed at a non-specialist, academic audience with interest in the international and environmental politics of sustainability and technology. This title is part of the Flip it Open Programme and may also be available Open Access. Check our website - Cambridge Core - for details.
What are gene drives?
28374Anonymous, MalariaGEN, 2023-11-09 09:43:47.
Among the new generation of technological tools being developed to combat malaria, there is a lot of buzz around gene drives. This is a method for genetically modifying malaria-spreading mosquitoes and ultimately reducing or replacing their populations. But how exactly do gene drives work? And how can genomic surveillance data produced by the MalariaGEN community help gene drive researchers achieve their goals safely and effectively?
Generating and testing reagents for CRISPR/Cas9 based homologous recombination and gene drive in Tribolium
28363C. M. Hannah, J. H. Kennedy, M. Megan, E. Z. Gabriel, W. Michael and Z. Andrew, bioRxiv, 2023.11.07.566100. 2023-11-08 09:45:24.
CRISPR/Cas9 gene drive systems are possible in a few insects and ever expanding. Nonetheless, success in one species and techniques developed for it are not necessarily applicable to other species. As such, the development and expansion of gene drive systems is dependent upon direct experimentation. A critical aspect and potentially limiting factor of gene drive is the ability to induce Cas9-dependent homologous recombination. Here we report our attempts to induce Cas9-dependent homologous recombination and subsequent gene drive in Tribolium castaneum. Utilizing constructs containing one or two target gRNAs in combination with Cas9 under two different promoters and corresponding homology arms, we found a high incidence of CRISPR/Cas9 induced mutations but a complete lack of evidence of homologous recombination and genetic drive. Even though the generated constructs provide new resources for CRISPR/Cas9 modification of the Tribolium genome, our results suggest that Tribolium genome may be refractory towards Cas9-induced homologous recombination and additional modifications will be necessary to increase the potential for homologous recombination.Competing Interest StatementThe authors have declared no competing interest.
Research breakthrough in genetic biocontrol striving to transform pest management: Centre for Invasive Species Solutions
28332ARR News, Australian Rural and Regional News, 2023-11-02 13:31:54.
A potential new non-lethal and ethical approach to control invasive mammal pests was showcased at a briefing held at the South Australian Health and Medical Research Institute in Adelaide on Tuesday 31 October. Hosted by the Centre for Invasive Species Solutions and the University of Adelaide, the briefing introduced guests to a world-first breakthrough in gene drive technology. The University of Adelaide discovery is the first time a new genetic tool has been identified that is able to induce female infertility into a mouse population, offering a non-lethal way to control mice and rats. Importantly, these findings could be transferred to control other pests, such as rabbits and feral cats.
Bill Gates Talks Gene Drives, mRNA, and U.S.$40m in Science Funding
28314N. Mlambo, allAfrica, 2023-10-31 08:32:46.
In 2003, the Bill and Melinda Gates Foundation launched the Grand Challenges initiative in order to find scientific solutions to these health challenges. Initially, the initiative focused on 14 scientific challenges including focusing on creating effective single-dose vaccines that can be used soon after birth, discovering drugs and delivery systems that minimise the likelihood of drug-resistant micro-organisms, creating therapies that can cure latent infection, and developing needle-free delivery systems. "We started Grand Challenges with two goals. In a narrow sense, we wanted to spur specific advances we thought could lead to breakthroughs. In 2003, we listed ... priorities like creating therapies that could cure latent TB infection - and supported researchers who had exciting ideas in those areas. In a broader sense, we hoped to inspire more brilliant scientists to share big ideas about transforming health in low-income countries. We hoped to create a scientific community that was supported to sustain R&D (Research and Development) for the benefit of billions of people who had been neglected," said co-chair of the Bill & Melinda Gates Foundation Bill Gates during his opening remarks at the Grand Challenges meeting held in Dakar, Senegal.
Genetic tools for conservation and health: What’s the Role of Gene Drive?
28313ISAAA, Institute of Agricultural Science for Southern Viet Nam, 2023-10-31 08:26:25.
The potential uses and impacts of gene drive technologies have garnered increasing interest at the international and national levels across the world. As part of the effort to contribute to an informed debate around gene drive technologies, the Outreach Network for Gene Drive Research and the ISAAA are organizing a new Gene Drive Webinar Series. The first webinar titled Genetic Tools For Conservation and Health: What's The Role of Gene Drives? is scheduled on November 16, 2023, 2 PM GMT+8. The registration is now open to all interested participants. The series is focused on specific countries and aims to promote a productive and balanced conversation on the benefits and risks of possible gene drive applications relevant to national priorities. Kicking off this series is the Philippines, a country that has consistently led biotechnology research and regulation in Asia, and is instrumental in shaping the region's perspectives on innovative technologies and scientific expertise. This first webinar will acquaint attendees with the fundamentals of gene drive and its significance for global health and conservation, presenting some of its prevailing applications under consideration.
Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops
28220A. Kormos, G. Dimopoulos, E. Bier, G. C. Lanzaro, J. M. Marshall and A. A. James, Frontiers in Bioengineering and Biotechnology, 11. 2023-10-26 14:54:57.
The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.
General science-technology orientation, specific benefit–risk assessment frame, and public acceptance of gene drive biotechnology
28225X. Liu, C. L. Goldsmith, K. E. Kang, A. Vedlitz, Z. N. Adelman, L. W. Buchman, E. Heitman and R. F. Medina, Risk Analysis, 2023-10-23 15:04:31.
Abstract With limited understanding of most new biotechnologies, how do citizens form their opinion and what factors influence their attitudes about these innovations? In this study, we use gene drive biotechnology in agricultural pest management as an example and theoretically propose that given low levels of knowledge and awareness, citizens? acceptance of, or opposition to, gene drive is significantly shaped by two predisposition factors: individuals? general orientation toward science and technology, and their specific benefit-risk assessment frame. Empirically, we employ data collected from a recent US nationally representative public opinion survey (N = 1220) and conduct statistical analyses to test the hypotheses derived from our theoretical expectations. Our statistical analyses, based on various model specifications and controlling for individual-level covariates and state-fixed effects, show that citizens with a more favorable general orientation toward science and technology are more likely to accept gene drive. Our data analyses also demonstrate that citizens? specific gene drive assessment frame?consisting of a potential benefit dimension and a potential risk dimension, significantly shapes their attitudes as well?specifically, people emphasizing more on the benefit dimension are more likely to accept gene drive, whereas those who place more importance on the risk dimension tend to oppose it. We discuss contributions of our study and make suggestions for future research in the conclusion.
Incorporating ecology into gene drive modelling
28150J. Kim, K. D. Harris, I. K. Kim, S. Shemesh, P. W. Messer and G. Greenbaum, Ecology Letters, 26:S62-S80. 2023-10-23 11:37:54.
Abstract Gene drive technology, in which fast-spreading engineered drive alleles are introduced into wild populations, represents a promising new tool in the fight against vector-borne diseases, agricultural pests and invasive species. Due to the risks involved, gene drives have so far only been tested in laboratory settings while their population-level behaviour is mainly studied using mathematical and computational models. The spread of a gene drive is a rapid evolutionary process that occurs over timescales similar to many ecological processes. This can potentially generate strong eco-evolutionary feedback that could profoundly affect the dynamics and outcome of a gene drive release. We, therefore, argue for the importance of incorporating ecological features into gene drive models. We describe the key ecological features that could affect gene drive behaviour, such as population structure, life-history, environmental variation and mode of selection. We review previous gene drive modelling efforts and identify areas where further research is needed. As gene drive technology approaches the level of field experimentation, it is crucial to evaluate gene drive dynamics, potential outcomes, and risks realistically by including ecological processes.
Benefits and risks of gene drives for invasive plant management – the case for common tansy
28162L. Croghan, A. G. Smith, M. A. Tancos, N. O. Anderson and R. L. Becker, Frontiers in Agronomy, 5. 2023-10-20 12:05:59.
Invasive plants cause significant environmental and economic damage, but land managers have few control options. Common tansy (Tanacetum vulgare) is prevalent in many US states and is one of the most reported invasive plants in Minnesota. Controlling common tansy poses a challenge due to its extensive distribution and association with diverse plant communities. A gene drive is being explored as a genetic biocontrol method for the management of several non-native invasives, including common tansy in North America. Gene drives have emerged as a novel biotechnology application with potential to improve public health, promote conservation, and increase agricultural productivity. In common tansy, gene drives could be developed to target genes that would reduce or eliminate female fertility and consequently inhibit common tansy seed production. Using common tansy as an example, we outline risks associated with the use of gene drive technology for invasive plant control and explain how risks may be mitigated. Understanding potential benefits and risks associated with gene drives in the early stages of development is crucial. Mitigating risks, receiving stakeholder input, and navigating the regulatory environment will play an important role in gene drive development and deployment.
How to fight insects that transmit diseases to people without harming those who cannot?
28157Nation World News Desk, Nation World, 2023-10-20 11:55:16.
One way to avoid this severe environmental impact is to specifically control the population of species that cause problems. This can be done chemically by releasing hormones into the environment that prevent passage to the adult stage, or pheromones that make them believe that a beautiful insect is waiting for them ready for sex, when in fact they fell in the trap of death. The problem with these methods is that sometimes the required molecules are very expensive and not always specific to what we want. A more effective strategy is to sterilize the population of male insects with radioactivity. In nature, these males mate with females, but cannot produce children. This technique has been used for a long time with reasonable results, although it is not 100% effective and the use of radioactivity means the appearance of mutations and it may happen (unlikely) that some give some development for the insect, and a recurring problem for us.However, genetic engineering offers us help. CRISPR/Cas9 is a technology that allows us to make specific changes in a specific area of the genome of any living organism. We can give it a twist and, instead of applying this technique to the genome of an insect by making a specific modification, what we do is modify an insect so that its genome has everything it needs to activate CRISPR/Cas9. time and cause sterility. It’s like hiding in your genome a complete CRISPR/Cas9 kit and the instructions to change a specific gene to create sterility. What is the advantage? If we only disperse the sterile males, those that are not sterile (sterilization is never 100% and we have to compete with the native population) will continue to reproduce, and in a few generations the effect will disappear.
Gene drive in plants emerges from infancy
28152M. J. A. Awan, R. Z. Naqvi, I. Amin and S. Mansoor, Trends in Plant Science, 2023-10-18 11:43:35.
Selfish genetic elements (SGEs) display biased transmission to offspring. However, their breeding potential has remained obscure. Wang et al. recently reported a natural gene-drive system that can be harnessed to prevent hybrid incompatibility and to develop a synthetic gene-drive (SGD) system for crop improvement.
Cleave and Rescue gamete killers create conditions for gene drive in plants
28140O. Georg, L. J. Michelle, I. Tobin and A. H. Bruce, bioRxiv, 2023.10.13.562303. 2023-10-14 10:23:38.
Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a DNA sequence-modifying enzyme such as Cas9/gRNAs (the Cleaver/Toxin) that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage (the Rescue/Antidote). ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. We demonstrate the essential features of ClvR gene drive in the plant Arabidopsis thaliana through killing of gametes that fail to inherit a ClvR that targets the essential gene YKT61, whose expression is required in male and female gametes for their survival. Resistant (uncleavable but functional) alleles, which can slow or prevent drive, were not observed. Modeling shows plant ClvRs can be used to rapidly drive population modification or suppression. Possible applications in weed control, plant breeding and conservation are discussed.Competing Interest StatementThe authors have filed patent applications on ClvR and related technologies (U.S. Application No. 15/970,728 and No. 16/673,823).
Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin-antidote gene drive that impairs pollen germination
28101L. Yang, J. Bingke, C. Jackson and Q. Wenfeng, bioRxiv, 2023.10.10.561637. 2023-10-11 07:52:15.
Synthetic gene drives, inspired by natural selfish genetic elements, present transformative potential for disseminating traits that benefit humans throughout wild populations, irrespective of potential fitness costs. Here, we constructed a gene drive system called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which employs a toxin-antidote mechanism in the male germline to override Mendelian inheritance in plants. Specifically, a gRNA-Cas9 cassette targets the essential No Pollen Germination 1 (NPG1) gene, serving as the toxin to block pollen germination. A recoded, CRISPR-resistant copy of NPG1 serves as the antidote, providing rescue only in pollen cells that carry the drive. To limit potential consequences of inadvertent release, we used self-pollinating Arabidopsis thaliana as a model. The drive demonstrated a robust 88-99% transmission rate over two successive generations, producing minimal resistance alleles that are unlikely to inhibit drive spread. Our study provides a strong basis for rapid genetic modification or suppression of outcrossing plant populations.Competing Interest StatementThe authors have declared no competing interest.
This Burkinabe researcher wants his groundbreaking work to wipe out malaria, altogether
28154B. Orucho and M. Ndengar, The African Mirror, 2023-10-10 11:49:04.
ABDOULAYE Diabaté and his team are betting on gene technology to protect children like his own from malaria. Along with a clutch of brand-new vaccines, the technology could help the world end malaria for good.
Genetically modified mosquitoes will be ready by 2033 – scientists
28096D. Sekayinga, MONITOR, 2023-10-10 07:43:26.
The Uganda Virus Research Institute (UVR[) has announced that genetically modified mosquitoes will be ready within a decade. Gene-drive mosquitoes are among the anti-malarial strategies the government under the Africa Target Malaria project has embarked on since 2016, to reduce the number of malaria deaths in the country. ''If the non -Gene-drive (sterilised) mosquitoes respond positively at every stage. we shall possibly be able to have the Gene-drives 10 years from now," Dr Jonathan Kayondo, one of the researchers, made the revelation during an anti-malarial training for journalists in Kalangala District last week. Dr Kayondo said every level of research will help in information flow, especially in places where research is conducted like the island of Jaana in Bubeke Sub-county in Kalangala District and Nsazi Island in Koome Sub-county. Mukono District. The two islands have high malaria cases. He added that researchers are yet to receive some Ugandan mosquito species whose genes have beenengineered at a laboratory in the USA for trial lease. "Ne are currently looking at developing sterile male mosquitoes that wouldn't be capable offertilising the female anopheles mosquitoes that spread malaria before introducing gene-drives to thecommunity," he said.
Expansions to the MGDrivE suite for simulating the efficacy of novel gene-drive constructs in the control of mosquito-borne diseases
28003J. B. Bennett, S. L. Wu, P. R. Chennuri, K. M. Myles and M. L. Ndeffo-Mbah, BMC Research Notes, 16:258. 2023-10-05 08:39:23.
The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strategies. Namely, current MGDrivE versions do not permit modeling of small molecule inducible systems for controlling gene expression in gene drive designs or the inheritance patterns of self-eliminating gene drive mechanisms. Here, we demonstrate a new MGDrivE 2 module that permits the simulation of gene drive strategies incorporating small molecule-inducible systems and self-eliminating gene drive mechanisms. Additionally, we also implemented novel sparsity-aware sampling algorithms for improved computational efficiency in MGDrivE 2 and supplied an analysis and plotting function applicable to the outputs of MGDrivE 1 and MGDrivE 2.
Mosquito Embryo Microinjection
27969R. A. Harrell, Cold Spring Harbor Protocols, 2023-10-03 07:27:01.
Genetically modified (GM) mosquitoes are an important tool in the fight against mosquito-borne disease, both indirectly through their use in research investigating host–pathogen interaction, mosquito olfaction, and anthropomorphic behavior and in future direct uses for suppression and possibly eradication through sterile insect technique (SIT) and/or gene-drive programs. Successful creation of GM mosquitoes depends on microinjection procedures that precisely deliver injection materials while causing as little damage to mosquito embryos as possible. Genetic modification reagents, such as transposon system components (vector plasmids, helper plasmids, and helper mRNA), and CRISPR–Cas9 components (guide RNAs, Cas9 protein, plasmids expressing Cas9 and/or guide RNAs, and donor plasmids used in homology-directed repair [HDR]), must be delivered into the preblastoderm embryo at the posterior end where the pole cells will form before cellularization occurs. Sharp needles that pierce the embryo easily are important tools in this procedure and work best when the embryos are not desiccated. The two main procedures for mosquito embryo microinjection involve injecting embryos under halocarbon oil or under aqueous solution.
Situating the social sciences in responsible innovation in the global south: the case of gene drive mosquitoes
28148K. Ledingham, C. Opesen, S. Hartley and S. Neema, Journal of Responsible Innovation, 10:2264100. 2023-10-01 11:32:46.
There has been growing attention in recent years on the potential reconfiguration of responsible innovation (RI) to increase its relevance for global challenges in the Global South. This reconfiguration will require a broad and empowered role for social scientists. Yet RI has been preoccupied with public and stakeholder inclusion, rather than social science inclusion. We probe this gap through a case study of the social sciences in the development of gene drive mosquitoes for malaria control in Mali and Uganda. Our data reveals potential diverse roles and future research agendas for the social sciences. We outline some challenges facing the social sciences in this space and ways to promote and support them. Lastly, we argue that RI?s predilection for reflexive and critical social science obscures a richer repertoire of social science roles that are an imperative and fundamental part of efforts to address global challenges in the Global South.
The Gamble: Can Genetically Modified Mosquitoes End Disease?
27985S. Nolen, New York Times, 2023-09-29 08:00:43.
The malaria situation in São Tomé and Príncipe, an African island nation with a population of 200,000, epitomizes the current challenge in the global struggle against the disease. The country is among the world’s least developed, and it has depended on foreign aid to fight malaria. Various campaigns over the past 50 years drove cases down, only to have them resurge worse than ever when the benefactor moved on. Over the past 18 years, with nearly $21 million from the Global Fund to Fight AIDS, Tuberculosis and Malaria, São Tomé has used a package of tools — including insecticide-treated bed nets; new and better drugs; killing larvae in bodies of water; and indoor spraying of homes — to stunning effect. No one has died of malaria here in the past five years. These countries need a way to fight the disease that is permanent and does not require continuous investment. Greg Lanzaro, a molecular geneticist at the University of California, Davis, who leads the malaria team, believes his grouphas that solution. “We’ve been working on this for 30 years, and from the beginning we said, ‘It has to work, but it also has to be inexpensive,and it has to be sustainable,’” he said as he watched the mosquitoes being released in a Santo Antonio park. “And we believewe have it.” But genetic modification is a controversial endeavor. Governments are hesitant, and few in Africa have laws to regulate theuse of the technology. Its risks lie in the unknowns: Could the modified mosquito evolve in some way that has harmfuleffects on the rest of the ecosystem? Could it prompt a dangerous mutation in the malaria parasite, which will find a new way to spread to survive? It is, in essence, the Jurassic Park question: Could meddling in genetic code have catastrophic consequences that no oneanticipates?
Engineered and natural gene drives: mechanistically the same, yet not same in kind
27995R. F. Medina and J. Kuzma, Nature Communications, 14:5994. 2023-09-26 08:18:08.
We propose the use of the terms natural gene drive (NGD) and engineered gene drive (EGD) arguing against James et al.1, who think both should be included within the term “gene drive”, based on their mechanistic similarities. Thanks to CRISPR-Cas-based gene editing, engineered gene drive has suddenly become feasible as a potential cost-effective pest control tool that could help us resolve wicked challenges2,3 . In nature, several organisms harbor genes that “selfishly” drive themselves into populations. This natural gene drive uses similar mechanisms to the ones use today to drive engineered genes into laboratory populations4 article we disagree with James et al.1 .In this who have recently proposed that because natural and engineered gene drives are mechanistically indistinguishable from a molecular standpoint, they should both be referred as “gene drives” because “a gene drive is a gene drive.” We instead propose that two terms be used to distinguish between natural and engineered gene drives, we second Wells and Steinbrecher5 arguments, and propose to use the terms natural gene drive (NGD) and engineered gene drive (EGD).
Could a new gene-editing technique be a major breakthrough in the battle against malaria?
27888B. Cottam, GEOGRAPHICAL, 2023-09-23 07:58:35.
The idea is that since female mosquitoes typically only mate once, the mass release of the sterile male mosquitoes should prevent wild females from producing future generations. Insect populations can and have already been successfully suppressed by the release of sterilised males that have been irradiated with gamma or x-rays, a technique that was originally trialled in the USA as a way to control agricultural pests such as fruit flies and screwworms. However, that method of sterilisation has a detrimental impact on the fitness of male mosquitoes, which then struggle to compete for mates with the wild males. That’s why sterilisation needs to be done genetically.
MGDrivE 3: A decoupled vector-human framework for epidemiological simulation of mosquito genetic control tools and their surveillance
27894A. Mondal, C. H. M. Sanchez and J. M. Marshall, bioRxiv, 2023.09.09.556958. 2023-09-12 08:11:56.
We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided.
A migration-selection model in genetic engineering
27690Y. Qi and L. Su, Nonlinear Analysis: Real World Applications, 75:103983. 2023-08-31 08:48:22.
We investigate a migration-selection system arising from CRISPR-Cas9 genetic engineering, which describes the evolution of the frequencies of a wild allele O, a drive allele D, and a brake allele B. The purpose is to see whether the drive allele D can persist in the population and whether its spread can be limited or stopped by the brake allele B when necessary. We give a complete classification of the dynamics of this system when there is no migration. We further show that migration may cause complex spatiotemporal patterns by demonstrating the existence of spatially inhomogeneous periodic solutions and steady state solutions.
Gene drives for invasive wasp control: Extinction is unlikely, with suppression dependent on dispersal and growth rates
27669P. J. Lester, D. O'Sullivan and G. L. W. Perry, Ecological Applications, 2023-08-24 06:36:30.
Abstract Gene drives offer a potentially revolutionary method for pest control over large spatial extents. These genetic modifications spread deleterious variants through a population and have been proposed as methods for pest suppression or even eradication. We examined the influence of local dispersal, long-distance and/or human-mediated dispersal, and variation in population growth, on the success of a gene drive for the control of invasive social wasps (Vespula vulgaris). Our simulations incorporated a spatially realistic environment containing variable habitat quality in New Zealand. Pest eradication was not observed, except in extreme and unrealistic scenarios of constant, widespread, and spatially intense releases of genetically modified individuals every year for decades. Instead, the regional persistence of genetically modified and wild-type wasps was predicted. Simulations using spatially homogeneous versus realistic landscapes (incorporating uninhabitable areas and dispersal barriers) showed little difference in overall population dynamics. Overall, little impact on wasp abundance was observed in the first 15?years post-introduction. After 25?years, populations were suppressed to levels <95% of starting populations. Populations exhibited ?chase dynamics? with population cycles in space, with local extinction occurring in some areas while wasps became abundant in others. Increasing the wasps' local dispersal distance increased the spatial and temporal variability of the occupied area and population suppression. Varying levels of human-associated long-distance dispersal had little effect on population dynamics. Increasing intrinsic population growth rates interacted with local dispersal to cause higher mean populations and substantially higher levels of variation in population suppression and the total amount of landscape occupied. Gene drives appear unlikely to cause a rapid and widespread extinction of this and probably other pests, but could offer long-term and cost-effective methods of pest suppression. The predicted level of <95% pest suppression would substantially reduce the predation pressure and competitive interactions of this invasive wasp on native species. However, the predicted long-term persistence of genetically modified pests will influence the ethics and likelihood of using gene drives for pest control, especially given concerns that modified wasps would eventually be transported back to their home range.
Optimizing the delivery of self-disseminating vaccines in fluctuating wildlife populations
27639C. Schreiner, A. Basinski, C. Remien and S. Nuismer, PLOS Neglected Tropical Diseases, 17:e0011018. 2023-08-18 07:45:43.
Author summary Pathogens such as Ebola, rabies, and Lassa virus that usually infect wildlife can jump to the human population. In the worst case, this can lead to outbreaks or pandemics such as happened in 2014 with Ebola and 2019 with SARS-CoV-2. One approach to mitigate the threat of pathogens spilling into the human population is to proactively vaccinate wildlife harboring these pathogens before the pathogens infect humans. With traditional vaccines, administering enough vaccines to the wildlife population to limit pathogen spread is challenging. To address this challenge, recent technological advances have allowed the development of vaccines that allow some degree of spread of the vaccine from animal to animal. However, for a vaccination campaign using these self-disseminating vaccines to be implemented successfully, we need to know when vaccines should be administered. We used mathematical models to explore how the reservoir host’s population ecology and properties of the vaccine affect the success of a vaccination campaign. Our results demonstrate that the timing of vaccine delivery relative to seasonal reproduction can make or break the success of vaccination programs. The effectiveness of self-disseminating vaccines is optimized by introducing vaccine after the peak of seasonal reproduction when the number of animals available for vaccination is highest.
Can Gene-Drives Combat Vector-Borne Diseases?
27636Anonymous, tomorrow.bio, 2023-08-18 07:40:46.
Scientists, technophiles, and the medical community are abuzz with a topic that sounds like science fiction: gene-drives. Given the growing fear of vector-borne diseases, wouldn’t it be marvelous if we could meddle with genetics to drive vectors like mosquitoes to extinction? Sounds too good to be true? Let’s dive into it! Understanding Gene-Drives To comprehend how gene-drives might revolutionize disease control, we first need to understand what they are. Think of gene-drives as inherently selfish genes that ensure their own propagation throughout a population, bypassing traditional inheritance rules of mother nature. Quite enjoyably sneaky, isn't it?
How genetically modifying mosquitoes could strengthen the world’s war on malaria
27634S. Oliver and J. Raman, The Conversation, 2023-08-18 07:35:58.
Mosquitoes can be genetically modified through two different technologies. The first method, paratransgenesis, involves infecting mosquitoes with bacteria that prevent them from transmitting malaria. This doesn’t harm the mosquito. It is important not to eliminate or harm mosquitoes because they pollinate many plants and are food for animals like bats, birds and reptiles. Scientists are excited about this method following the recent discovery of a bacterium that occurs naturally in mosquitoes’ guts and appears to prevent the malaria parasite from developing inside the mosquito. The second method involves genetically modifying the mosquitoes themselves. This approach centres on gene drives: genetic systems that ensure genes of interest are inherited by all offspring in every generation. There are two types of gene drive. One aims to reduce the vector population size and is known as population suppression. The other aims to prevent the mosquito from transmitting malaria; it is known as population modification.
Single-cell profiling of Anopheles gambiae spermatogenesis defines the onset of meiotic silencing and premeiotic overexpression of the X chromosome
27624N. Page, C. Taxiarchi, D. Tonge, J. Kuburic, E. Chesters, A. Kriezis, K. Kyrou, L. Game, T. Nolan and R. Galizi, Commun Biol, 6:850. 2023-08-15 10:04:13.
Understanding development and genetic regulation in the Anopheles gambiae germline is essential to engineer effective genetic control strategies targeting this malaria mosquito vector. These include targeting the germline to induce sterility or using regulatory sequences to drive transgene expression for applications such as gene drive. However, only very few germline-specific regulatory elements have been characterised with the majority showing leaky expression. This has been shown to considerably reduce the efficiency of current genetic control strategies, which rely on regulatory elements with more tightly restricted spatial and/or temporal expression. Meiotic silencing of the sex chromosomes limits the flexibility of transgene expression to develop effective sex-linked genetic control strategies. Here, we build on our previous study, dissecting gametogenesis into four distinct cell populations, using single-cell RNA sequencing to define eight distinct cell clusters and associated germline cell-types using available marker genes. We reveal overexpression of X-linked genes in a distinct cluster of pre-meiotic cells and document the onset of meiotic silencing of the X chromosome in a subcluster of cells in the latter stages of spermatogenesis. This study provides a comprehensive dataset, characterising the expression of distinct cell types through spermatogenesis and widening the toolkit for genetic control of malaria mosquitoes.
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria
27626A. Qureshi and J. B. Connolly, Malaria Journal, 22:234. 2023-08-14 10:10:18.
Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity.
Proposed Changes to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines)
27609National Institutes of Health, Federal Register, 2023-08-10 08:09:09.
The National Institutes of Health (NIH) seeks input on a proposal to revise the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) to include specific considerations and requirements for conducting research involving gene drive modified organisms (GDMO) in contained research settings. NIH is proposing to update the NIH Guidelines to clarify minimum containment requirements, propose considerations for performing risk assessments, and define additional institutional responsibilities regarding Institutional Biosafety Committees (IBCs) and Biosafety Officers (BSOs). The proposed revisions are specific to GDMO research subject to the NIH Guidelines, conducted in contained settings and are consistent with the recommendations of the NIH Novel and Exceptional Technology Research Advisory Committee report, Gene Drives in Biomedical Research (NExTRAC Report). NIH does not currently support research involving potential field release of GDMOs and the NIH Guidelines pertain to contained research; accordingly, no changes regarding potential field release are being proposed in this Notice. NIH is also proposing revisions to the NIH Guidelines to harmonize with the Biosafety in Microbiological and Biomedical Laboratories (BMBL), 6th edition regarding the Risk Group (RG) categorization of West Nile Virus (WNV) and Saint Louis Encephalitis Virus (SLEV).
Mosquitoes spread malaria. These researchers want them to fight it instead
26948G. Brumfiel, NPR, 2023-07-20 08:45:44.
Mosquitoes carry malaria, which kills hundreds of thousands of people each year. Now some researchers are trying to use genetic engineering to make the pesky insects into allies in the fight against the disease. The approach is a radical departure from traditional ways of controlling malaria. For years, public health officials have tried to limit the disease by controlling mosquito populations. But that approach is temporary, says Anthony James, a professor of molecular biology and genetics at the University of California, Irvine. Because mosquitoes are extremely tough little insects, and their populations can quickly rebound. "To try to get rid of them, I don't think it's possible," he says. Instead, James and his colleagues want to try a different approach: making mosquitoes themselves into malaria-fighting warriors.
Mosquito-friendly gene drive may lead to a malaria-free future
26945Anonymous, LIFE TECHNOLOGY, 2023-07-19 08:23:51.
A gene drive is a genetic mechanism that allows a particular gene to spread rapidly through a population. In the case of malaria, scientists are working on developing a gene drive that would make mosquitoes resistant to the parasite that causes the disease. This would reduce the number of mosquitoes that can transmit the disease to humans. However, there are concerns about the use of gene drives. One potential issue is that the gene drive could spread beyond the intended population of mosquitoes and affect other species. Another concern is that the gene drive could have unintended consequences, such as creating new diseases or disrupting ecosystems. To address these concerns, scientists are developing a new type of gene drive that is "mosquito-friendly." This means that the gene drive would only affect mosquitoes that carry the malaria parasite, rather than all mosquitoes. This would reduce the risk of unintended consequences and help to ensure that the gene drive is effective in reducing the spread of malaria.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
26903C. Weizhe, G. Jialiang, L. Yiran and C. Jackson, bioRxiv, 2023.07.17.549342. 2023-07-17 11:00:13.
Gene drive alleles, which bias their own inheritance and increase in frequency, show great promise for blocking disease transmission or directly suppressing pest populations. The most common engineered drive system is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after CRISPR cleavage. One successful homing drive example targets a female-specific exon in doublesex in Anopheles mosquitos, suppressing the population by inducing recessive sterility in female drive homozygotes. We found that in Drosophila melanogaster, a 3-gRNA drive disrupting the doublesex female exon resulted in a masculine phenotype and dominant female sterility. Resistance alleles formed by end-joining repair were also dominant sterile. This was likely caused by expression of male-specific transcripts in females with drive and resistance alleles, disrupting sex development. Based on this construct, we proposed a new pest suppression system called Release of Insects carrying a Dominant-sterile Drive (RIDD). This entails continuously releasing drive heterozygous males, with drive and resistance alleles causing sterility in females. The drive remains at high frequency longer than currently used dominant female-lethal alleles (RIDL) due to drive conversion in males, and drive alleles also cause sterility based on resistance, both substantial advantages. With weekly releases of drive males into a cage population with overlapping generations, our RIDD system targeting dsx reached 100% prevalence within 27 weeks, progressively reducing egg production and eventually causing total population collapse. RIDD combines the merits of homing gene drive and RIDL. It is powerful but self-limiting, unlike unconfined standard homing drives, allowing for targeted population suppression.Competing Interest StatementThe authors have declared no competing interest.
New germline Cas9 promoters show improved performance for homing gene drive
26623D. Jie, C. Weizhe, J. Xihua, X. Xuejiao, Y. Emily, Z. Ruizhi, Z. Yuqi, M. Matt, W. M. Philipp and C. Jackson, bioRxiv, 2023.07.16.549205. 2023-07-16 08:48:12.
Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives, perhaps the most powerful gene drive strategy, convert wild type alleles into drive alleles in heterozygotes with the help of Cas9 and gRNA. However, achieving successful outcomes with these drives often requires high performance. Specifically, it is desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. Thus far, high-performance promoters have only been discovered in Anopheles species. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we tested eleven Drosophila melanogaster germline promoters in several configurations. Some of the new promoters achieved higher drive conversion efficiency with minimal embryo resistance, but none could completely avoid somatic expression like nanos. However, such somatic expression often did not carry detectable fitness costs when the promoter-Cas9 elements supported a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Based on our findings, we selected two Cas9 promoter lines for cage experiments with a 4-gRNA suppression drive. While one promoter exhibited substantial somatic effects, leading to a low drive equilibrium frequency, the other outperformed nanos, resulting in the successful suppression of the cage population. Overall, these novel Cas9 promoters hold potential advantages for homing drives in Drosophila species and may also possess valuable homologs in other organisms.Competing Interest StatementThe authors have declared no competing interest.
Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
26580R. Carballar-Lejarazú, Y. Dong, T. B. Pham, T. Tushar, R. M. Corder, A. Mondal, H. M. Sánchez C, H.-F. Lee, J. M. Marshall, G. Dimopoulos and A. A. James, Proceedings of the National Academy of Sciences, 120:e2221118120. 2023-07-11 05:52:31.
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)?based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.
Mosquitoes made immune to malaria could help stamp out the disease
26614C. Wilson, NewScientist, 2023-07-10 13:29:44.
Mosquitoes have been gene edited so they are immune to the parasites that cause malaria. If released into the wild, the genetic modification should spread through a population of mosquitoes because it contains a sequence known as a “gene drive”, which means all the modified insects’ offspring would inherit the immunity. This approach could slash the numbers of malaria cases in people. Malaria is one of the world’s leading causes of death and ill health, taking a particular toll on young children in sub-Saharan Africa. Two vaccines have recently been developed, but they only give partial immunity. Other high-tech strategies against mosquito-borne diseases are under investigation, including gene drives that kill all mosquitoes in a targeted area. But these could have unpredictable effects on ecosystems, says Anthony James at the University of California, Irvine.
Routes of Introduction of Anopheles gambiae Into Remote Islands in the Indian Ocean
26612R. E. Ditter, M. Campos, M. W. Crepeau, J. Pinto, A. Toilibou, Y. Amina, Y. Lee, A. J. Cornel and G. C. Lanzaro, 2023-07-07 13:23:28.
The malaria vector Anopheles gambiae s.s., is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between island and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. We investigated the source population of A. gambiaefor each island, determined the number of introductions and estimated when they occurred, and explored evidence for contemporary gene flow between island and mainland populations. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and that there is no evidence of contemporary migration between the islands and mainland Africa. This study further supports the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
Unleashing the swarm: Battling the global mosquito menace and defending public health
26467J. Entine and S. Moxon, Genetic Literacy Project, 2023-07-05 07:47:22.
There is one solution embraced by global health experts that should be pursued aggressively, if with some caution. Scientists in real-world trials have altered the genomes of entire animal populations, including mosquitoes, to thwart the vectoring of diseases and control pests — an innovation called gene drives. Emerging gene drive technologies offer enormous potential and have already shown their value in test projects in many parts of the world. More recently, the application of CRISPR/Cas9 tools has dramatically accelerated their effectiveness. But implementation on a wider scale is progressing at a snail’s pace. Why? For the most part, it is restrained by controversy, misunderstanding and the political opposition of activist environmental groups in Europe and North America.
Guerrilla eugenics: gene drives in heritable human genome editing
26475A. D. Cutter, J Med Ethics, 2023-07-04 08:15:56.
CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome editing. Modification gene drives applied to heritable human genome editing would introduce a novel form of involuntary eugenic practice that I term guerrilla eugenics. Once introduced into a genome, stealth genetic editing by a gene drive genetic element would occur each subsequent generation irrespective of whether reproductive partners consent to it and irrespective of whether the genetic change confers any benefit. By overriding the ability to 'opt in' to genome editing, gene drives compromise the autonomy of carrier individuals and their reproductive partners to choose to use or avoid genome editing and impose additional burdens on those who hope to 'opt out' of further genome editing. High incidence of an initially rare gene drive in small human communities could occur within 200 years, with evolutionary fixation globally in a timeframe that is thousands of times sooner than achievable by non-drive germline editing. Following any introduction of heritable gene drives into human genomes, practices intended for surveillance or reversal also create fundamental ethical problems. Current policy guidelines do not comment explicitly on gene drives in humans. These considerations motivate an explicit moratorium as being warranted on gene drive development in heritable human genome editing.
Steering and controlling evolution — from bioengineering to fighting pathogens
26463M. Lässig, V. Mustonen and A. Nourmohammad, Nature Reviews Genetics, 2023-07-03 07:31:07.
Control interventions steer the evolution of molecules, viruses, microorganisms or other cells towards a desired outcome. Applications range from engineering biomolecules and synthetic organisms to drug, therapy and vaccine design against pathogens and cancer. In all these instances, a control system alters the eco-evolutionary trajectory of a target system, inducing new functions or suppressing escape evolution. Here, we synthesize the objectives, mechanisms and dynamics of eco-evolutionary control in different biological systems. We discuss how the control system learns and processes information about the target system by sensing or measuring, through adaptive evolution or computational prediction of future trajectories. This information flow distinguishes pre-emptive control strategies by humans from feedback control in biotic systems. We establish a cost–benefit calculus to gauge and optimize control protocols, highlighting the fundamental link between predictability of evolution and efficacy of pre-emptive control.
Novel Conservation Strategies to Conserve Australian Marsupials
28144S. Legge, M. Hayward and A. Weeks, American and Australasian Marsupials, 2023-07-01 10:36:55.
The Australian marsupial fauna has been devastated in the past 250 years, mainly due to impacts from invasive mammalian predators (cats and foxes), although other threats such as invasive herbivores, habitat loss and fragmentation, changes to fire regimes, and now climate change have played a role. The profound and ongoing impact of invasive predators has driven substantial research and management innovation. Australia has been at the forefront of developing approaches to reduce the density and impacts of introduced predators and implementing novel and ambitious species conservation programs. A large and growing network of islands and mainland fenced areas, free of introduced predators (“havens”), has been critical for avoiding further species extinctions. Outside these havens, advances in toxin presentation and deployment have enabled cat and fox densities to be reduced over large areas. Substantial research and field trials have been carried out to understand how predator-prey interactions, and habitat quality management, can be used to reduce predation impacts on susceptible native species. Synthetic biology offers new opportunities to manage introduced predators, including potentially by using gene drives. Finally, the attenuation of the formerly large continuous ranges of many species to small, isolated population remnants (because of predation or other reasons) has also driven research and improvements in genetic and metapopulation management that will increase the chance of population persistence in the longer term. However, unless Australia continues to invest in research and innovative conservation actions, the plight of its priceless marsupial fauna will remain perilous.
Off Target: Gene Drives and the Balance of Life
26295Save Our Seeds, 2023-06-28 09:25:43.
This is a compilation of conversations with experts about gene drive technologies and the science/social questions it raises.
Scientists are Gene-Editing Flies to Fight Crop Damage
26310E. Mullin, WIRED, 2023-06-28 07:28:35.
In greenhouses in Oregon last month, researchers with the US Department of Agriculture began testing one such approach: sterilized male flies. The gene-edited bugs, made by St. Louis–based biotech company Agragene, are meant to suppress wild fly populations. The idea is that if they were to be released into the environment, the sterilized males would mate with wild females, resulting in a fertility dead end. “We see this technology as being able to provide healthier fruit and vegetables without doing a lot of harm to the environment,” says Agragene CEO Bryan Witherbee. Scientists at the company used the DNA editing tool Crispr to knock out two essential genes in fly embryos—one involved in male reproduction and another with female development. As a result, only sterile males hatch while the females die. “You don’t want to release females into the population, because those are the ones that are doing the damage,” says Stephanie Gamez, director of research and development at Agragene.
How genetically modified mosquitoes could eradicate malaria
26308S. Jones, Nature, 2023-06-28 07:16:33.
Malaria is caused by Plasmodium parasites that are transmitted from person to person by Anopheles mosquitoes — often Anopheles gambiae, the primary vector in sub-Saharan Africa. Many approaches to malaria control focus on mosquitoes. Insecticide-treated mosquito nets and indoor spraying of insecticides, for instance, have played a massive part in malaria reduction. But still it persists. “We’ve had great success over the past 20 years, using the bed nets and spraying, but those tools are not going to be enough to eliminate malaria,” says Gregory Lanzaro, director of the Vector Genetics Laboratory at the University of California, Davis. Many researchers, including Lanzaro, are hopeful that part of the solution lies in altering the genomes of Anopheles mosquitoes. Scientists around the world are exploring how to make lasting changes to mosquito DNA that impair the insects’ ability to transmit malaria — either by making them less hospitable hosts to Plasmodium, or by interfering with their reproduction to reduce or eliminate mosquito populations. Interventions of this kind have been in development for decades, but their use in the wild could be now just years away. Ecological and ethical concerns, however, about how these modified mosquitoes will be monitored, and by whom, remain the subject of active and contentious conversation.
MGSurvE: A framework to optimize trap placement for genetic surveillance of mosquito population
26616C. H. Sánchez, D. L. Smith and J. M. Marshall, bioRxiv, 2023-06-23 13:35:51.
Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible - ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii)an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is freely available as an open-source Python package on pypi ( https://pypi.org/project/MGSurvE/ ). It is intended as a resource for both field and computational researchers interested in mosquito gene surveillance. AUTHOR SUMMARY: Mosquito-borne diseases such as malaria and dengue fever continue to pose a major health burden throughout much of the world. The impact of currently-available tools, such as insecticides and antimalarial drugs, is stagnating, and gene drive-modified mosquitoes are considered a novel tool that could contribute to continuing reductions in disease transmission. Gene drive approaches are unique in the field of vector control in that they involve transgenes that could potentially spread on a wide scale, and consequently, surveillance is expected to be a major cost driver for the technology. This is needed to monitor for unintended spread of intact drive alleles, and the emergence of alternative alleles such as homing-resistance alleles and non-functional effector genes. Additionally, surveillance of insecticide-resistance alleles is of interest to support the impact of insecticide-based tools such as bednets. Here, we present MGSurvE, a computational framework that optimizes trap placement for genetic surveillance of mosquito populations in order to minimize the time to detection for an allele of interest. MGSurvE has been tailored to various features of mosquito ecology, and is intended as a resource for researchers to optimize the efficiency of limited surveillance resources.
CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus
25865T. Harvey-Samuel, X. Feng, E. M. Okamoto, D.-K. Purusothaman, P. T. Leftwich, L. Alphey and V. M. Gantz, bioRxiv, 2023.06.12.544656. 2023-06-15 08:40:13.
Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test the first CRISPR-based homing gene drive for Culex quinquefasciatus, demonstrating the possibility of using this technology to control Culex mosquitoes. Our results show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes
CRISPR/Cas9-based split homing gene drive targeting doublesex for population suppression of the global fruit pest Drosophila suzukii
25710A. K. Yadav, C. Butler, A. Yamamoto, A. A. Patil, A. L. Lloyd and M. J. Scott, Proc Natl Acad Sci U S A, 120:e2301525120. 2023-06-13 10:38:33.
Genetic-based methods offer environmentally friendly species-specific approaches for control of insect pests. One method, CRISPR homing gene drive that target genes essential for development, could provide very efficient and cost-effective control. While significant progress has been made in developing homing gene drives for mosquito disease vectors, little progress has been made with agricultural insect pests. Here, we report the development and evaluation of split homing drives that target the doublesex (dsx) gene in Drosophila suzukii, an invasive pest of soft-skinned fruits. The drive component, consisting of dsx single guide RNA and DsRed genes, was introduced into the female-specific exon of dsx, which is essential for function in females but not males. However, in most strains, hemizygous females were sterile and produced the male dsx transcript. With a modified homing drive that included an optimal splice acceptor site, hemizygous females from each of the four independent lines were fertile. High transmission rates of the DsRed gene (94 to 99%) were observed with a line that expressed Cas9 with two nuclear localization sequences from the D. suzukii nanos promoter. Mutant alleles of dsx with small in-frame deletions near the Cas9 cut site were not functional and thus would not provide resistance to drive. Finally, mathematical modeling showed that the strains could be used for suppression of lab cage populations of D. suzukii with repeated releases at relatively low release ratios (1:4). Our results indicate that the split CRISPR homing gene drive strains could potentially provide an effective means for control of D. suzukii populations.
To fight berry-busting fruit flies, researchers focus on sterilizing the bugs
25719M. Walling, KTAL News.com, 2023-06-13 09:42:56.
Paul Nelson is used to doing battle with an invasive fruit fly called the spotted wing drosophila, a pest that one year ruined more than half the berries on the Minnesota farm he and his team run. In recent years, they’ve cut their losses closer to 5%, but it’s been labor-intensive and expensive. “It’s a pest that if you’re not willing to stick the time into it, it’s going to take over your farm,” said Nelson, the head grower at Untiedt’s, a vegetable and fruit operation about an hour west of Minneapolis. Nelson and other growers may someday get a new tool as a result of research at North Carolina State University into the insects, which ruin the berries by laying their eggs in them and have been estimated to cost growers hundreds of millions of dollars annually. The researchers, using a concept called “gene drive,” manipulated the insects’ DNA so that the female offspring would be sterile, and the method they used to achieve it significantly reduced the chance that a population could rebound.
CRISPR/Cas9-based gene drive could suppress agricultural pests
25706North Carolina State University, Phys Org, 2023-06-12 10:22:37.
Researchers have developed a "homing gene drive system" based on CRISPR/Cas9 that could be used to suppress populations of Drosophila suzukii vinegar flies—so-called "spotted-wing Drosophila" that devastate soft-skinned fruit in North America, Europe and parts of South America—according to new research from North Carolina State University. The NC State researchers developed dual CRISPR gene drive systems that targeted a specific D. suzukii gene called doublesex, which is important for sexual development in the flies. CRISPR stands for "clustered regularly interspaced short palindromic repeats" and Cas9 is an enzyme that performs like molecular scissors to cut DNA. CRISPR systems are derived from bacterial immune systems that recognize and destroy viruses and other invaders, and are being developed as solutions to problems in human, plant and animal health, among other uses. Targeting the doublesex gene resulted in female sterility in numerous experiments as females were unable to lay eggs, says Max Scott, an NC State entomologist who is the corresponding author of a paper in Proceedings of the National Academy of Sciences that describes the research. "This is the first so-called homing gene drive in an agricultural pest that potentially could be used for suppression," Scott said. Gene drives can preferentially select, change or delete particular traits or characteristics and "drive" those edits through future generations, resulting in a sometimes far greater than 50% chance of passing those changes to progeny.
The attitudes of young adults towards mammalian predator control and Predator Free 2050 in Aotearoa New Zealand
26186L. Dickie and F. Medvecky, Australasian Journal of Environmental Management, 2023-06-09 12:31:11.
Predator Free 2050 (PF2050) is an ambitious goal that aims to remove three types of invasive mammals from New Zealand by 2050. It will require a significant amount of funding, research, and support. Young adults will have an important role to play for this programme to be successful. Therefore, understanding the awareness and attitudes of young adults towards PF2050, and predator control, is an essential consideration. A survey of 1479 18- to 24-year-olds was conducted in 2017. The results showed that a higher percentage of young adults than members of the broader public view the small, introduced mammals as threats to New Zealand’s environment. Furthermore, this study highlights support for the control of feral, stray, and domestic cats. More focused research on attitudes towards cats is recommended to gauge which control methods are approved of by young adults. Indeed, methods appear to be a key factor to young adults supporting PF2050. The aerial distribution of poison was largely viewed negatively, and moderate concern was expressed about the targeted animal’s welfare. Interestingly, young adults appeared to be open to the use of gene editing and gene drive, although they expressed caution. Targeted communication towards young adults on toxins and genetic methods is recommended. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products
26281S. L. James, H. Quemada, M. Q. Benedict and B. Dass, Frontiers in Bioengineering and Biotechnology, 11:1205865. 2023-06-08 10:56:02.
Gene drive-modified mosquitoes (GDMMs) are proposed as new tools for control and elimination of malaria and other mosquito-borne diseases, and promising results have been observed from testing conducted in containment. Although still at an early stage of development, it is important to begin now to consider approval procedures and market entry strategies for the eventual implementation of GDMMs in the context of disease control programs, as these could impact future research plans. It is expected that, as for other types of new products, those seeking to bring GDMMs to market will be required to provide sufficient information to allow the regulator(s) to determine whether the product is safe and effective for its proposed use. There already has been much emphasis on developing requirements for the biosafety components of the "safe and effective" benchmark, largely concerned with their regulation as genetically modified organisms. Other potential approval requirements have received little attention, however. Although GDMMs are expected to be implemented primarily in the context of public health programs, any regulatory analogies to other public health products, such as pharmaceuticals, vaccines, or chemical pesticides, must take into account the characteristics of live mosquito products. Typical manufacturing standards related to product identity, potency or quality will need to be adapted to GDMMs. Valuable lessons can be drawn from the regulatory approval processes for other whole organism and genetically modified (GM) organism products. Supply chain requirements, such as scale of production, location and design of production facilities, and methods of distribution and delivery, will be dependent upon the characteristics of the particular GDMM product, the conditions of use, and the region to be served. Plans for fulfilling supply chain needs can build upon experience in the development of other live insect products for use in public health and agriculture. Implementation of GDMMs would benefit from additional research on enabling technologies for long-term storage of mosquito life stages, efficient mass production, and area-wide delivery of GDMMs. Early consideration of these practical requirements for market entry will help to mitigate downstream delays in the development of these promising new technologies.
Generation game: gene-edited mosquitos to fight malaria
25551J. Opara, Sci Dev Net, 2023-06-07 08:44:49.
Population-level changes in the genetic make-up of one of the world’s deadliest animals could provide a key in the fight against malaria, proponents of a radical new technology argue. So-called gene drive technology, where genetic changes are passed down through generations, could rein in mosquito populations, or prevent them from passing on malaria.“Through genetic engineering, researchers have modified mosquitoes to favour the inheritance of genes that either will reduce the size of the population of those mosquitoes or stop them from transmitting the malaria parasite,” Michael Santos, senior vice-president and chief population health sciences officer at the US-based charity the Foundation for the National Institutes of Health (FNIH), tells SciDev.Net. “In other words, [it is about] using mosquitoes to control mosquitoes.” Malaria is one of the world’s “big three” deadly diseases, killing over half a million people in 2021, the vast majority in Africa.
A framework for identifying fertility gene targets for mammalian pest control
25416C. C. Anna, A. Alana, E. Rey, E. Kevin, K. Sebastian, D. Ludovic, C. Jackson, E. C. Samuel, W. M. Philipp and J. G. Neil, bioRxiv, 2023.05.30.542751. 2023-06-01 07:38:46.
Fertility-targeted gene drives have been proposed as an ethical genetic approach for managing wild populations of vertebrate pests for public health and conservation benefit. This manuscript introduces a framework to identify and evaluate target gene suitability based on biological gene function, gene expression, and results from mouse knockout models. This framework identified 16 genes essential for male fertility and 12 genes important for female fertility that may be feasible targets for mammalian gene drives and other non-drive genetic pest control technology. Further, a comparative genomics analysis demonstrates the conservation of the identified genes across several globally significant invasive mammals. In addition to providing important considerations for identifying candidate genes, our framework and the genes identified in this study may have utility in developing additional pest control tools such as wildlife contraceptives.Competing Interest StatementThe authors have declared no competing interest.
CRISPR-based gene editing of non-homologous end joining factors biases DNA repair pathway choice toward single-strand annealing in Aedes aegypti
25461K. Chae, J. M. Overcash, C. Dawson, C. Valentin, H. Tsujimoto, K. M. Myles and Z. N. Adelman, Current Research in Biotechnology, 5:100133. 2023-05-29 08:04:22.
To maintain genome stability, eukaryotic cells orchestrate DNA repair pathways to process DNA double-strand breaks (DSBs) that result from diverse developmental or environmental stimuli. Bias in the selection of DSB repair pathways, either non-homologous end joining (NHEJ) or homology-directed repair (HDR), is also critical for efficient gene editing and for homing-based gene drive approaches developed for the control of disease-transmitting vector mosquitoes. However, little is understood about DNA repair homeostasis in the mosquito genome. Here, we utilized CRISPR/Cas9 to generate indel mutant strains for core NHEJ factors ku80, DNA ligase IV (lig4), and DNA-PKcs in the mosquito Aedes aegypti and evaluated the corresponding effects on DNA repair. In a plasmid-based assay, disruption of ku80 or lig4, but not DNA-PKcs, reduced both NHEJ and SSA. However, a transgenic reporter strain-based test revealed that those mutations significantly biased DNA repair events toward SSA. Interestingly, ku80 mutation also significantly increased the end joining rate by a yet-characterized mechanism in males. Our study provides evidence that the core NHEJ factors have an antagonistic effect on SSA-based DSB repair of the Ae. aegypti genome. Down-modulating the NHEJ pathway can enhance the efficiency of nuclease-based genetic control approaches, as most of those operate by homology-based repair processes along with extensive DNA end resection that is antagonized by NHEJ.
Adaptation in the face of internal conflict: the paradox of the organism revisited
25238M. M. Patten, M. A. Schenkel and J. A. Ågren, Biological Reviews, 2023-05-19 07:37:20.
The paradox of the organism refers to the observation that organisms appear to function as coherent purposeful entities, despite the potential for within-organismal components like selfish genetic elements and cancer cells to erode them from within. While it is commonly accepted that organisms may pursue fitness maximisation and can be thought to hold particular agendas, there is a growing recognition that genes and cells do so as well. This can lead to evolutionary conflicts between an organism and the parts that reside within it. Here, we revisit the paradox of the organism. We first outline its conception and relationship to debates about adaptation in evolutionary biology. Second, we review the ways selfish elements may exploit organisms, and the extent to which this threatens organismal integrity. To this end, we introduce a novel classification scheme that distinguishes between selfish elements that seek to distort transmission versus those that seek to distort phenotypic traits. Our classification scheme also highlights how some selfish elements elude a multi-level selection decomposition using the Price equation. Third, we discuss how the organism can retain its status as the primary fitness-maximising agent in the face of selfish elements. The success of selfish elements is often constrained by their strategy and further limited by a combination of fitness alignment and enforcement mechanisms controlled by the organism. Finally, we argue for the need for quantitative measures of both internal conflicts and organismality.
Leveraging eco-evolutionary models for gene drive risk assessment
25157M. A. Combs, A. J. Golnar, J. M. Overcash, A. L. Lloyd, K. R. Hayes, D. A. O’Brochta and K. M. Pepin, Trends in Genetics, 2023-05-15 15:09:00.
As development of gene drive systems accelerates and diversifies, predicting outcomes for target populations and the potential for human and environmental risks requires accounting for numerous eco-evolutionary processes.Gene drive dynamic models quantify the influence of features across genetics (e.g., resistance development and standing genetic diversity), demographics (e.g., mating systems and inbreeding), spatial ecology (e.g., dispersal and competition), biotic and abiotic environments (e.g., climate variation and landscape structure), and implementation strategies (e.g., introduction size and timing) on gene drive outcomes.Synthesizing published gene drive models reveals research trends, knowledge gaps, and emergent principles. Modeling limitations and tradeoffs are discussed.Integrating an iterative modeling approach within the existing phased pathway for gene drive research improves utility for risk assessment.
Rapid, scalable, combinatorial genome engineering by marker-less enrichment and recombination of genetically engineered loci in yeast
26189M. Abdullah, B. M. Greco, J. M. Laurent, R. K. Garge, D. R. Boutz, M. Vandeloo, E. M. Marcotte and A. H. Kachroo, Cell Rep Methods, 3:100464. 2023-05-10 12:35:58.
A major challenge to rationally building multi-gene processes in yeast arises due to the combinatorics of combining all of the individual edits into the same strain. Here, we present a precise and multi-site genome editing approach that combines all edits without selection markers using CRISPR-Cas9. We demonstrate a highly efficient gene drive that selectively eliminates specific loci by integrating CRISPR-Cas9-mediated double-strand break (DSB) generation and homology-directed recombination with yeast sexual assortment. The method enables marker-less enrichment and recombination of genetically engineered loci (MERGE). We show that MERGE converts single heterologous loci to homozygous loci at ∼100% efficiency, independent of chromosomal location. Furthermore, MERGE is equally efficient at converting and combining multiple loci, thus identifying compatible genotypes. Finally, we establish MERGE proficiency by engineering a fungal carotenoid biosynthesis pathway and most of the human α-proteasome core into yeast. Therefore, MERGE lays the foundation for scalable, combinatorial genome editing in yeast.
Mathematical modeling of the performance of wild and transgenic mosquitoes in malaria transmission
25861A. P. Wyse, A. J. B. dos Santos, J. D. Azevedo, A. C. de Meneses and V. M. D. Santos, Plos One, 18:23. 2023-04-28 08:20:19.
A mathematical model that simulates malaria transmission under the influence of transgenic mosquitoes refractory to malaria is presented in this paper. The zygosity of transgenic mosquitoes is taken into account and, consequently, the total population of mosquitoes is comprised of wild type and heterozygous and homozygous transgenic mosquitoes. These three mosquito varieties interact by mating and competition, and the genetic characteristics of their resulting offspring are in accordance with Mendelian genetics or the mutagenic chain reaction (MCR) technique. Although the incorporation of transgenic mosquitoes into the ecosystem reduces the incidence of malaria, the model also takes into account the importance of completing treatment in individuals with confirmed infection and the imminent risk of increased environmental temperature.
Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages
25086A. Simoni, R. D'Amato, C. Taxiarchi, M. Galardini, A. Trusso, R. Minuz, S. Gilli, A. Somerville, D. Shittu, A. Khalil, R. Galizi and R. Muller, Research Square, 2023-04-24 06:46:30.
CRISPR-based gene drives have the potential to spread within a population and are considered as promising vector control tools. A doublesex-targeting gene drive was shown effective to suppress laboratory populations in both small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework demand for systems able to modulate or revert the action of gene drives, as part of post-release risk-mitigation plans. We developed an improved AcrIIA4-based anti-drive strain and showed inhibition of gene drive spread, in complex feeding and reproductive behavioural conditions. A stochastic model predicted the experimentally-observed genotypes dynamics in overlapping generations in medium- and large-sized cages and further demonstrated the effectiveness of anti-drive in different release and fitness scenarios. This study provides a further validation for the use of anti-drive system in controlling the spread of gene drive in Anopheles under complex behavioural conditions.
Gene Drives as Interventions into Nature: the Coproduction of Ontology and Morality in the Gene Drive Debate
25114K. Boersma, B. Bovenkerk and D. Ludwig, NanoEthics, 17:4. 2023-04-22 10:10:41.
Gene drives are potentially ontologically and morally disruptive technologies. The potential to shape evolutionary processes and to eradicate (e.g. malaria-transmitting or invasive) populations raises ontological questions about evolution, nature, and wilderness. The transformative promises and perils of gene drives also raise pressing ethical and political concerns. The aim of this article is to arrive at a better understanding of the gene drive debate by analysing how ontological and moral assumptions are coproduced in this debate. Combining philosophical analysis with a critical reading of the gene drive literature and an ethnographic study of two leading research groups, the article explores the hypothesis that the development of and debate about gene drives are characterized by a particular intervention-oriented mode of coproduction. Based on the results of this exploration, we highlight the need for a broadening of the perspective on gene drives in which empirical, moral, and ontological concerns are addressed explicitly in their interplay rather than in (disciplinary) isolation from each other.
Defining transformation events for gene drive in species complexes
25001J. B. Connolly, IOBC-WPRS Bulletin, 163:8-20. 2023-04-13 15:11:40.
Engineered gene drives (EGDs) that allow the super-Mendelian inheritance of genetic traits could one day be used to reduce the vectorial capacity of Anopheles species that transmit human malaria in Africa. Many Anopheles species belong to complexes of closely related sibling species that can produce fertile interspecific hybrid females. In cases where the genomic target locus of the EGD is conserved amongst sibling species from the same complex as the released target species, it would therefore be plausible that the EGD could be vertically transmitted from the target species to sibling species by interspecific mating. To differentiate genetically modified organisms, the term ‘transformation event’ is used, based on the specific genomic location of the transgenic construct, as a result of random genomic integration. In contrast, an EGD is generated via its precise and reproducible insertion in its specific genomic target locus. These considerations pose two key questions for the use of EGD in species complexes: (i) what does the definition of “transformation event” mean in the context of vertical gene drive transfer of the EGD to sibling species in species complexes and (ii) does de novo transformation of an EGD into a sibling species constitute the same transformation event as introgression by backcrossing into a sibling species of an EGD that had been originally transformed in the target species? While definitions of the term transformation event that have been provided by national and intergovernmental organisations are somewhat ambiguous, they do provide scope for broad interpretation of vertical gene drive transfer of a specific EGD to different sibling species of the target species as the same transformation event. There also appears to be some consensus that definitions of transformation event support the notion that de novo transformations of an EGD in sibling species constitute the same transformation events as introgression by backcrossing into sibling species of an EGD that had been originally inserted in the target species.
In The Face Of Nigerian Mosquito Nets, Westerners’ Gene Editing Offers Hope
24964O. Onwumere, The Nigerian Voice, 2023-04-10 10:42:21.
In Nigeria, the utilization of mosquito nets is prevalent, while in the Western world, optimism is associated with the implementation of gene editing technology. In this article, ODIMEGWU ONWUMERE reports that malaria could soon be eradicated in Nigeria. According to US scientists, Anopheles mosquitoes have been genetically modified to resist the malaria-causing parasite by incorporating various anti-malaria molecules that target different stages of the parasite's lifecycle. Nevertheless, the article highlights a lack of information on the knowledge and overall viewpoint of Nigerian scientists concerning GMMs
Modelling the effect of migration on the localisation and spread of a gene drive
24955C. Benjamin James and F.-L. Alexandre Jules Hen, bioRxiv, 2023.04.02.535303. 2023-04-04 14:22:19.
Gene drives have the potential to address pressing ecological issues. Through the super-Mendelian inheritance of a gene drive, a trait can be spread through a population even in spite of a fitness cost. This ability to spread is both its greatest quality and detractor. We may not want a gene drive to spread universally. If a gene drive were designed to cause the collapse of a pest population, it may inadvertently cause the collapse of the entire species. Migration is the mechanism through which a gene drive can spread to distant populations. Understanding its effect on the progression of a gene drive is crucial to our ability to control a gene drive. While migration can spread the gene drive to other populations, equally it can bring in other alleles to the population that may disrupt the progression of the gene drive. Through our deterministic migration gene drive model we can assess the conditions in which a gene drive is likely to spread to unintended populations, and if a gene drive is likely to be displaced by incoming alleles.Competing Interest StatementThe authors have declared no competing interest.
First transgenic mosquito made in Africa by Transmission Zero
24962H. Dunning, Imperial College London, 2023-04-04 10:33:04.
Transmission Zero, a global scientific programme led by scientists at Imperial College London and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), announces the generation of the first transgenic mosquito strain ever to be made in Africa.This strain carries in its genome genetic modifications that will allow scientists in the future to render mosquitoes unable to transmit malaria. This major scientific achievement is a pivotal milestone in the renewed international efforts to rid Africa of malaria. Half of the world’s population is at risk of contracting malaria, a disease caused by parasites that are transmitted from one person to another through mosquito bites. In 2021 alone, there were over 247 million cases and 619,000 deaths from malaria, mostly children under five years old in sub-Saharan Africa.
A gene drive is a gene drive: the debate over lumping or splitting definitions
24910S. L. James, D. A. O'Brochta, F. Randazzo and O. Akbari, Nature Communications, 2023-03-29 12:22:20.
Gene drive technologies are being considered as a new approach to address a variety of currently intractable global problems, including to prevent disease transmission, reduce crop loss, and preserve biodiversity1. There are some outside the genetics research community who argue that wide use of the term “gene drive” to encompass selfish genetic elements found either in extant organisms (natural gene drives) or assembled in the laboratory (synthetic gene drives) will discourage the necessary scrutiny of risks that may be associated with the introduction of synthetic gene drives into free-living populations of target organisms2,3. Here we argue that the current definition is both scientifically sound and promotes good governance.
Evolution driven by genetic engineering should be known as ‘genetic welding’ to draw scientific and ethical scrutiny
24940S. Moore, AZO Life Sciences, 2023-03-29 10:13:27.
The advent of CRISPR-Cas9 technology has been revolutionary, but it has also been highly controversial. In an opinion paper published in the journal Trends in Genetics, evolutionary geneticist Asher Cutter highlights the importance of coining the term ‘genetic welding’ for the anthropogenic manipulation of genetic drive made possible by tools such as CRISPR-Cas9. Separating this process from other processes that influence evolution might be fundamental to ensuring proper consideration is given to the potential future outcomes of genetic welding.
The Promise and Challenge of Genetic Biocontrol Approaches for Malaria Elimination
24901S. James and M. Santos, Tropical Medicine and Infectious Disease, 2023-03-29 07:50:09.
Malaria remains an ongoing public health challenge, with over 600,000 deaths in 2021, of which approximately 96% occurred in Africa. Despite concerted efforts, the goal of global malaria elimination has stalled in recent years. This has resulted in widespread calls for new control methods. Genetic biocontrol approaches, including those focused on gene-drive-modified mosquitoes (GDMMs), aim to prevent malaria transmission by either reducing the population size of malaria transmitting mosquitoes or making the mosquitoes less competent to transmit the malaria parasite. The development of both strategies has advanced considerably in recent years, with successful field trials of several biocontrol methods employing live mosquito products and demonstration of the efficacy of GDMMs in insectary-based studies. Live mosquito biocontrol products aim to achieve area-wide control with characteristics that differ substantially from current insecticide-based vector control methods, resulting in some different considerations for approval and implementation. The successful field application of current biocontrol technologies against other pests provides evidence for the promise of these approaches and insights into the development pathway for new malaria control agents. The status of technical development as well as current thinking on the implementation requirements for genetic biocontrol approaches are reviewed, and remaining challenges for public health application in malaria prevention are discussed.
What should we call evolution driven by genetic engineering? Genetic welding, says researcher
24897Cell Press, Phys Org, 2023-03-28 07:29:32.
With CRISPR-Cas9 technology, humans can now rapidly change the evolutionary course of animals or plants by inserting genes that can easily spread through entire populations. Evolutionary geneticist Asher Cutter proposes that we call this evolutionary meddling “genetic welding.” In an opinion paper publishing March 28 in the journal Trends in Genetics, he argues that we must scientifically and ethically scrutinize the potential consequences of genetic welding before we put it into practice.
Synthetic gene drives as an anthropogenic evolutionary force
24895A. D. Cutter, Trends in Genetics, 2023-03-28 07:24:22.
Genetic drive represents a fundamental evolutionary force that can exact profound change to the genetic composition of populations by biasing allele transmission. Herein I propose that the use of synthetic homing gene drives, the human-mediated analog of endogenous genetic drives, warrants the designation of ‘genetic welding’ as an anthropogenic evolutionary force. Conceptually, this distinction parallels that of artificial and natural selection. Genetic welding is capable of imposing complex and rapid heritable phenotypic change on entire populations, whether motivated by biodiversity conservation or public health. Unanticipated possible long-term evolutionary outcomes, however, demand further investigation and bioethical consideration. The emerging importance of genetic welding also compels our explicit recognition of genetic drive as an addition to the other four fundamental forces of evolution.
Gene Drives Are Coming
24887D. Lowe, Science, 2023-03-23 08:26:31.
Consider the “gene drive” idea - there are a lot of variations, but the general idea is that you introduce a genetic sequence into an organism that can bias (drive) its own inheritance into the next generation. This is a thumb-on-the-scale unnatural selection if ever there was one, because that biased inheritance is outside of any fitness advantage that the new sequence might bring with it. In fact, a number of gene drive ideas have the opposite sign, conferring catastrophic unfitness in order to wipe out pathogens and disease-vector organisms.Gene drives of various kinds show up in nature, though, when a gene has some sort of ability to control its own transmission. These are the so-called “selfish genes”, and some of these have no fitness advantage (or even some disadvantage) in the organisms themselves. There are a lot of potential mechanisms for this (see that link for a good review), but what you don’t see are the total-wipeout forms just mentioned, which is what we has humans might like to do to (say) mosquitos or tsetse flies. The advent of CRISPR-Cas9 technology has really brought a lot more attention to these ideas, because they make them far more possible, for better or worse.
Identification and functional analysis of Cochliomyia hominivorax U6 gene promoters
27884R. Novas, T. Basika, M. E. Williamson, P. Fresia, A. Menchaca and M. J. Scott, Insect Molecular Biology, 2023-03-21 08:32:32.
The New World screwworm, Cochliomyia hominivorax, is an obligate parasite, which is a major pest of livestock. While the sterile insect technique was used very successfully to eradicate C. hominivorax from North and Central America, more cost-effective genetic methods will likely be needed in South America. The recent development of CRISPR/Cas9-based genetic approaches, such as homing gene drive, could provide a very efficient means for the suppression of C. hominivorax populations. One component of a drive system is the guide RNA(s) driven by a U6 gene promoter. Here, we have developed an in vivo assay to evaluate the activity of the promoters from seven C. hominivorax U6 genes. Embryos from the related blowfly Lucilia cuprina were injected with plasmid DNA containing a U6-promoter-guide RNA construct and a source of Cas9, either protein or plasmid DNA. Activity was assessed by the number of site-specific mutations in the targeted gene in hatched larvae. One promoter, Chom U6_b, showed the highest activity. These U6 gene promoters could be used to build CRISPR/Cas9-based genetic systems for the control of C. hominivorax.
Gene Drives: Target Malaria is underestimating the risks
24867C. Then, Testbiotech, 2023-03-17 07:55:56.
The Target Malaria consortium has for several years been planning to conduct field trials using genetically engineered mosquitoes in Burkina Faso. The aim is to transfer artificial gene constructs, i. e. the so-called ‘X-shredder’, into wild populations of the mosquitoes. This gene construct is meant to reduce the number of female offspring, and thus bring about a decline in the overall population of mosquitoes (Anopheles gambiae) known to transmit malaria. However, as recent research shows, the planned releases are based on flawed data and incorrect assumptions.
Regulatory and policy considerations for the implementation of gene drive-modified mosquitoes to prevent malaria transmission
24859S. L. James, B. Dass and H. Quemada, Transgenic Research, 32:17. 2023-03-15 15:00:05.
Gene drive-modified mosquitoes (GDMMs) are being developed as possible new tools to prevent transmission of malaria and other mosquito-borne diseases. To date no GDMMs have yet undergone field testing. This early stage is an opportune time for developers, supporters, and possible users to begin to consider the potential regulatory requirements for eventual implementation of these technologies in national or regional public health programs, especially as some of the practical implications of these requirements may take considerable planning, time and coordination to address. Several currently unresolved regulatory questions pertinent to the implementation of GDMMs are examined, including: how the product will be defined; what the registration/approval process will be for placing new GDMM products on the market; how the potential for transboundary movement of GDMMs can be addressed; and what role might be played by existing multinational bodies and agreements in authorization decisions. Regulation and policies applied for registration of other genetically modified organisms or other living mosquito products are assessed for relevance to the use case of GDMMs to prevent malaria in Africa. Multiple national authorities are likely to be involved in decision-making, according to existing laws in place within each country for certain product classes. Requirements under the Cartagena Protocol on Biodiversity will be considered relevant in most countries, as may existing regulatory frameworks for conventional pesticide, medical, and biocontrol products. Experience suggests that standard regulatory processes, evidence requirements, and liability laws differ from country to country. Regional mechanisms will be useful to address some of the important challenges.
Assessing the hybridization potential between a hypothetical gene drive-modified Drosophila suzukii strain and non-target Drosophila species
24990J. Romeis, S. Wolf, J. Collatz, J. Enkerli and F. Widmer, IOBC-WPRS Bulletin, 163:108. 2023-03-13 14:49:23.
Genetically engineered gene drives (GD) are a potentially powerful tool to control pest insects by population suppression or even elimination. Before living GD modified insects can be released into the environment, they must pass an environmental risk assessment (ERA). A key question to be addressed is the potential acquisition of functional GD elements by nontarget species as this may lead to the loss of those species and to a disruption of the ecosystem services they provide. The main route for gene flow is through hybridization between the GD insect strain and closely related species that co-occur in the area of release. Using the invasive Drosophila suzukii as a case study, we demonstrate how the potential for hybridization can be assessed.
CRISPR-based genetic control strategies for insect pests
24978Y. Yan, R. A. Aumann, I. Hacker and M. F. Schetelig, Journal of Integrative Agriculture, 22:651-668. 2023-03-11 07:53:08.
Genetic control strategies such as the sterile insect technique have successfully fought insect pests worldwide. The CRISPR (clustered regularly interspaced short palindromic repeats) technology, together with high-quality genomic resources obtained in more and more species, greatly facilitates the development of novel genetic control insect strains that can be used in area-wide and species-specific pest control programs. Here, we review the research progress towards state-of-art CRISPR-based genetic control strategies, including gene drive, sex ratio distortion, CRISPR-engineered genetic sexing strains, and precision-guided sterile insect technique. These strategies' working mechanisms, potential resistance development mechanisms, and regulations are illustrated and discussed. In addition, recent developments such as stacked and conditional systems are introduced. We envision that the advances in genetic technology will continue to be one of the driving forces for developing the next generation of pest control strategies.
Gene Drives and Vector-Borne Diseases: A Comparative Perspective Using Malaria as a Case Study
24818S. Todi, The Takshashila Institution, 2023-03-07 15:51:15.
Gene drives are an emerging technological application to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. This method for vector control is currently at the research stage, with parallel community engagement programmes being carried out in African countries to raise awareness for its adoption. Yet, the risks associated with using gene drives may go beyond the communities they are deployed in. Hence, it is critical for India to understand the relevance of gene drive application in India and its neighboring countries to create effective policy measures for achieving control of vector-borne diseases. Using malaria as a case study, we argue that India currently does not require the use of gene drives to achieve control of mosquito-borne diseases. However, India should invest in research for gene drives and vaccines, while continuing with current efforts to curb vector-borne diseases. Further, India will need strong data monitoring systems to identify if any gene drive mosquitoes deployed by other countries make their way to India.
Hybrid incompatibilities in the anopheles gambiae species complex
24968A. Kriezis, Imperial College London, 2023-03-01 10:47:20.
Malaria is an infectious disease caused by parasites of the genus Plasmodium which is responsible for approximately 400,000 deaths annually, primarily in sub-Saharan Africa. Malaria is transmitted by mosquitoes belonging to the Anopheles gambiae species complex. While progress has been made to reduce the incidence of malaria, the emergence of insecticide resistance necessitates the development of novel vector control strategies. Gene drive technologies have seen significant advances in recent years, providing hope for their implementation in the near future. While gene flow has been identified between sibling species of the An. gambiae species complex, they are reproductively isolated by both pre- and post-zygotic isolation mechanisms. Interspecific crosses between most member species produce sterile hybrid males, in accordance with Haldane’s rule of speciation. The aim of this project was to support the development of gene drive technologies by investigating hybrid incompatibilities between two of the most significant vector species, Anopheles gambiae and Anopheles arabiensis. The potential for the introgression of genomic regions from one species into the genetic background of the other was investigated to help inform models regarding the spread of gene drives between sibling species. In addition, the identification of genetic elements involved in hybrid male sterility could provide potential targets for vector control strategies. Large autosomal regions were found to introgress and persist in interspecific genomes without a detectable fertility cost. In addition, the introduction of distinct autosomal regions of conspecific DNA into otherwise heterospecific genomes of hybrid males was found to overcome hybrid incompatibilities and partially restore fertility. While no specific genetic factors involved in hybrid incompatibilities could be identified, the results indicate that such factors are present at least on the X chromosome. Furthermore, the evidence suggests that asynapsis between interspecific homologous autosomes during gametogenesis plays a role in the manifestation of hybrid male sterility.
Alleviating the burden of malaria with gene drive technologies? A biocentric analysis of the moral permissibility of modifying malaria mosquitoes
24800N. de Graeff, K. R. Jongsma and A. L. Bredenoord, Journal of Medical Ethics, 2023-02-28 08:33:28.
Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor's biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor's egalitarian biocentrism.
Engagement on risk assessment for gene drive mosquitoes by EFSA and Target Malaria
24794S. Hartley, A. Kokotovich, Y. Devos and J. Mumford, Environmental Science and Policy, 142:183-193. 2023-02-27 11:12:07.
As engineered gene drive technologies continue to advance, many actors are actively considering how environmental risk assessments (RAs) for gene drive organisms should be conducted, and how stakeholder engagement opportunities should be provided. There is, however, a lack of clarity concerning what constitutes engagement on gene drive RA and, furthermore, what forms of engagement already exist around gene drive RA. To address this gap, we reflect on the actions of a risk assessor (the European Food Safety Authority, EFSA) and a gene drive developer (Target Malaria) to understand: 1) the RA-related decisions that each are making concerning gene drive technology for mosquitoes and other harmful insects, 2) the existing role of engagement in those decisions, and 3) the implications for our understandings of engagement and RA. We found, first, that both EFSA and Target Malaria have already made many RA-related decisions, even though any preparation and evaluation of a formal RA for gene drive mosquitoes remains far off. This finding supports the idea that gene drive RA involves multiple processes and decisions in different forms across the entire technology and regulatory development process. Second, we found that both EFSA and Target Malaria have already integrated engagement into their respective RA-related decisions in different ways, reflecting their different roles. We conclude by considering how EFSA and Target Malaria could improve their existing RA-related engagement by explicitly considering disciplinary diversity and worldview diversity in their related decision making.
A toxin-antidote CRISPR gene drive system for regional population modification
24826J. Champer, E. Lee, E. Yang, C. Liu, A. G. Clark and P. W. Messer, Nature Communications, 11:1082. 2023-02-27 10:39:13.
Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. Here, we introduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target. Modeling shows that such drives will have threshold-dependent invasion dynamics, spreading only when introduced above a fitness-dependent frequency. We demonstrate a TARE drive in Drosophila with 88-95% transmission by female heterozygotes. This drive was able to spread through a large cage population in just six generations following introduction at 24% frequency without any apparent evolution of resistance. Our results suggest that TARE drives constitute promising candidates for the development of effective, flexible, and regionally confinable drives for population modification.
Simulations Reveal High Efficiency and Confinement of a Population Suppression CRISPR Toxin-Antidote Gene Drive
24791Y. Zhu and J. Champer, ACS Synthetic Biolog, 2023-02-24 09:56:44.
Though engineered gene drives hold great promise for spreading through and suppressing populations of disease vectors or invasive species, complications such as resistance alleles and spatial population structure can prevent their success. Additionally, most forms of suppression drives, such as homing drives or driving Y chromosomes, will generally spread uncontrollably between populations with even small levels of migration. The previously proposed CRISPR-based toxin-antidote system called toxin-antidote dominant embryo (TADE) suppression drive could potentially address the issues of confinement and resistance. However, it is a relatively weak form of drive compared to homing drives, which might make it particularly vulnerable to spatial population structure. In this study, we investigate TADE suppression drive using individual-based simulations in a continuous spatial landscape. We find that the drive is actually more confined than in simple models without space, even in its most efficient form with low cleavage rate in embryos from maternally deposited Cas9. Furthermore, the drive performed well in continuous space scenarios if the initial release requirements were met, suppressing the population in a timely manner without being severely affected by chasing, a phenomenon in which wild-type individuals avoid the drive by recolonizing empty areas. At higher embryo cut rates, the drive loses its ability to spread, but a single, widespread release can often still induce rapid population collapse. Thus, if TADE suppression gene drives can be successfully constructed, they may play an important role in control of disease vectors and invasive species when stringent confinement to target populations is desired.
GeneConvene Global Collaborative Webinar Series | Emerging Gene Drive Systems 2023
24769David O'Brochta, 2023-02-22 15:50:48.
Gene drive systems are being engineered in the laboratory and in some cases shown to be effective at rapidly altering target-gene frequencies in experimental populations. Much of this foundational work has been conducted in insects in the laboratory. This webinar series will focus on emerging potential applications of gene drive technology in a wide variety of organisms. These webinars are intended to inform audiences of the rationale for these development efforts, the current state of research and development and outstanding challenges.
Gene Drive Technology With Agricultural Application Potential
24788R. Carmeli-Peslak, SeedWorld, 2023-02-22 09:51:36.
Gene drive technology, a genetic phenomenon that occurs in nature, causes a trait to spread in species through sexual reproduction over many generations. The inheritance rate is higher than the Mendelian rate which is 50%. Gene drives have been used for public health and conservation, but can potentially be used in multiple species, like agricultural pests according to a release. Weeds and pests have a negative impact on crops and their impact has caused interest in potentially using genetic techniques, like gene drive, to help control weeds and pests. Current insect pest control includes the use of pesticides which has helped to decrease food loss and waste. Research around new tools will help continue to protect crops and reduce food waste while also minimizing agriculture’s environmental footprint. These new tools and practices include gene editing techniques. Now in its early stages, gene-drive-based strategies are being research to help reduce agricultural pests. The gene-drive-based strategies will focus on both controlling pests that cause damage and spreading desired crop or livestock traits faster. A limitation with this strategy is that gene drives cannot work on asexually reproducing organisms. The strategy is also unsuitable for species that have longer generation times. While gene-drive-based strategies may not meet all the needs, but it is a helpful tool to continue to investigate.
Will new genetic engineering tech finally eliminate malaria?
24747Anonymous, Business Daily, 2023-02-20 19:03:20.
Richard Mukabana, a senior research and policy analyst at African Institute for Development Policy, says the technology which employs the principle of sending a thief to catch a thief may yet prove the most effective. “It is only a mosquito that knows where another mosquito is and it’s easier for it to search for others and kill them through suppression,” says Prof Mukabana. In gene drive technologies, an artificial gene is introduced into the malaria-transmitting mosquito population. This then disrupts reproduction by either distorting sex chromosome inheritance such that most offspring are males, or by knocking out female fertility genes such that they no longer lay eggs. Experts argue that the current technology used in fighting malaria, which comprises vector control and drug therapy has not been sufficiently adequate to eliminate the disease on the continent, hence the need to embrace new technologies.
Next-generation CRISPR gene-drive systems using Cas12a nuclease
24783S. Sanz Juste, E. M. Okamoto, X. Feng and V. L. Del Amo, bioRxiv, 2023.02.20.529271. 2023-02-20 09:40:53.
One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of novel gene drive arrangements. Yet, other nucleases such as the temperature-sensitive Cas12a have not been explored for gene drive designs. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.Competing Interest StatementAll authors declare no competing interests.
How genomics can help biodiversity conservation
24754K. Theissinger, C. Fernandes, G. Formenti, I. Bista, P. R. Berg, C. Bleidorn, A. Bombarely, A. Crottini, G. R. Gallo, J. A. Godoy, S. Jentoft, J. Malukiewicz, A. Mouton, R. A. Oomen, S. Paez, P. J. Palsbøll, C. Pampoulie, M. J. Ruiz-López, S. Secomandi, H, Trends in Genetics, 2023-02-16 19:11:36.
Genomics provides effective tools to characterize biodiversity, but the full implementation of genomic techniques in practical conservation is still limited. We review some of the main approaches in biodiversity genomics available to conservationists and genomicists.High-quality, long-read sequencing and bioinformatic technologies facilitate genome sequencing and assembly for any species. We summarize how reference genomes, in conjunction with population genomic data, can contribute to biodiversity monitoring, conservation, and restoration efforts.Over the past decade, many initiatives to generate reference genomes spanning the tree of life have emerged worldwide. We call for increased integration of reference genomes and population genomics data into interdisciplinary conservation efforts to fully unlock the potential of genomics in safeguarding global biodiversity.
Gene Drive: Past, Present and Future Roads to Vertebrate Biocontrol
24780G. R. McFarlane, C. B. A. Whitelaw and S. G. Lillico, Applied Biosciences, 2:52-70. 2023-02-13 09:35:36.
Scientists have long sought a technology to humanely control populations of damaging invasive pests in a species-specific manner. Gene drive technology could see this become a reality. This review charts the twists and turns on the road to developing gene drives in vertebrates. We focus on rodents, as these will likely be the first targets, and trace the journey from the early understanding of selfish genetic elements to engineering gene drives in mice; before discussing future research focuses and the crucial role that public perception and governance will play in the application of this technology. The realisation of robust gene drive strategies in vertebrate pests has the potential to revolutionise biocontrol.
Review of gene drive modelling and implications for risk assessment of gene drive organisms
24722J. L. Frieß, C. R. Lalyer, B. Giese, S. Simon and M. Otto, Ecological Modelling, 478:110285. 2023-02-13 09:34:10.
Synthetic gene drive (GD) systems constitute a form of novel invasive environmental biotechnology with far-reaching consequences beyond those of other known genetically modified organisms (GMOs). During the last 10 years, the development of GD systems has been closely linked to mathematical modelling which can provide feedback on how to achieve gene drive spread but also may be used to predict the ecological consequences of a gene drive release. GMOs, thus also GD systems, need to pass an environmental risk assessment (ERA) prior to a release into the environment. Models in this respect may play an important role because a release of GD organisms, even at a small scale, may not be reversible. In our review, we analyse the scope and structure of existing models to examine how they may assist the ERA. Our analysis reveals that a majority of models so far are deterministic, non-spatial and not tailored for a specific target organism. Models often use simplified assumptions on the biology of the species and seem to be made to test the effectiveness of the drive. Few models go beyond this and verify whether model predictions may be realistic under field conditions. We identified four advanced models that we judged to be the most ecologically realistic and compared the implemented parameters with ERA requirements by the European Food Safety Authority (EFSA) and World Health Organization (WHO) for genetically modified insects and mosquitoes. Although a number of abiotic and biotic factors are already considered in these models, mating-related factors and traits relevant to the interactions between the GMO and target organisms and with other species are largely excluded. Overall, our results show that biological and ecological realism are still poorly realized in current models and that most models aim to predict efficacy rather than ecological effects. Given the complexity of natural ecosystems, it may not be possible to compile a single model to cover all complexities. Thus, models should be further developed with the purpose to assist specific questions related to the risk assessment of GDs. Moreover, uncertainty will be a key issue for any model used in RA and we see the need to improve this aspect when modelling gene drives.
The Anthropocene as the End of Nature? Why Recognizing Interventionism Is Key in Coming to Terms with the Anthropocene
24729K. Boersma, ENVIRONMENTAL ETHICS, 44:195-219. 2023-02-12 09:43:02.
In this article, I address and argue against the tendency to understand the anthropocene as inaugurating the end of nature. I conduct two key moves. First, by way of an engagement with the concept of anthropocene technology I explain how understanding the anthropocene as the end of nature prevents us from recognizing what the anthropocene is all about: interventionism. Secondly, I illustrate how a nondualist understanding of the human-nature relation allows us to recognize interventionism as the hallmark of the anthropocene without falling back into the hierarchical human-nature conceptions that underlie interventionism. A nondualist framework that conserves the human-nature distinction helps us in our ability to relate critically to contemporary science and technology in the anthropocene. I illustrate the conceptual narrative of the article through the specific case of gene drive technology development.
Introducing Emerging Health Technologies in Africa
24724Health Tech Africa, Health Tech Africa Podcast, 2023-02-08 14:22:59.
In this episode, the Project Director of the Platform for Dialogue and Action on Health Technologies in Africa, Professor Richard Mukabana, discusses new technologies that if well developed and proven safe and effective, have enormous potential to eradicate disease on the continent.
Social justice environmental activists move to block gene editing to control invasive species and promote biodiversity. Here’s why they’re misguided
24701S. Smyth, Genetic Literacy Project, 2023-02-07 12:46:02.
Control of invasive species has been extremely difficult with eradication virtually impossible. To control invasive plant species, chemicals are commonly used while in some instances removal of plants by hand, as Shiva advocates, is undertaken. Efforts to control invasive animals include poisoning and shooting. Needless to say, these ‘control techniques’ are inefficient and often harmful to the applicators. Advances in genetics potentially offer new solutions, using gene editing technology to create sterile populations. Sterility is a natural trait in mammals, which can be induced into invasive animals as a means of population control. Invasive pests can be captured, gene-edited to confer sterility in future generations and then released back into the wild. The offspring will gradually without the use of chemicals or hand labor contribute to reduced populations. Applying gene editing technologies is not an instantaneous solution, but they may be part of a long-term strategy.
Biopolitik: The Promise of Gene Drive
24708S. Todi, Technopolitik, 2023-02-07 09:57:49.
Gene drives are genetic elements of an organism that are transmitted to progeny at higher than mendelian frequencies (>50%). Gene editing techniques such as CRISPR–Cas9 have made gene drives extremely efficient in laboratory settings and have shown the potential to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. Research in gene drives, especially on mosquitoes, is being carried out by scientists at the University of California, San Diego, Texas A&M University, and Massachusetts Institute of Technology, among others. However, concerns have been raised regarding the potential unintended consequences, especially in terms of the ecological impact of gene-drive systems.
Assessing potential hybridization between a hypothetical gene drive-modified Drosophila suzukii and nontarget Drosophila species
24610S. Wolf, J. Collatz, J. Enkerli, F. Widmer and J. Romeis, Risk Analysis, 2023-01-24 09:02:35.
Genetically engineered gene drives (geGD) are potentially powerful tools for suppressing or even eradicating populations of pest insects. Before living geGD insects can be released into the environment, they must pass an environmental risk assessment to ensure that their release will not cause unacceptable harm to non-targeted entities of the environment. A key research question concerns the likelihood that nontarget species will acquire the functional GD elements; such acquisition could lead to reduced abundance or loss of those species and to a disruption of the ecosystem services they provide. The main route for gene flow is through hybridization between the geGD insect strain and closely related species that co-occur in the area of release and its expected dispersal. Using the invasive spotted-wing drosophila, Drosophila suzukii, as a case study, we provide a generally applicable strategy on how a combination of interspecific hybridization experiments, behavioral observations, and molecular genetic analyses can be used to assess the potential for hybridization.
Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements
24581M. A. E. Anderson, E. Gonzalez, J. X. D. Ang, L. Shackleford, K. Nevard, S. A. N. Verkuijl, M. P. Edgington, T. Harvey-Samuel and L. Alphey, Nature Communications, 14:338. 2023-01-20 09:00:46.
CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. While attempts have been made to develop such systems in Aedes aegypti, none have been able to match the high drive efficiency observed in Anopheles species. Here we generate Ae. aegypti transgenic lines expressing Cas9 using germline-specific regulatory elements and assess their ability to bias inheritance of an sgRNA-expressing element (kmo(sgRNAs)). Four shu-Cas9 and one sds3-Cas9 isolines can significantly bias the inheritance of kmo(sgRNAs), with sds3G1-Cas9 causing the highest average inheritance of ~86% and ~94% from males and females carrying both elements outcrossed to wild-type, respectively. Our mathematical model demonstrates that sds3G1-Cas9 could enable the spread of the kmo(sgRNAs) element to either reach a higher (by ~15 percentage point) maximum carrier frequency or to achieve similar maximum carrier frequency faster (by 12 generations) when compared to two other established split drive systems.
Gene Drives Could Fight Malaria and Other Global Killers but Might Have Unintended Consequences
24460M. Cobb, Scientific American, 2023-01-13 08:22:55.
Every year more than 600,000 people die from mosquito-transmitted malaria, most of them children under age five. Some insects that are disease vectors, such as mosquitoes, are currently expanding their range around the world, bringing new threats. Genetic engineering can fix this by permanently altering insect genes through what is known as a gene drive. This technology allows a chosen set of genes to alter an animal’s biology in some way, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the laws of inheritance. The genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, their careful use might save millions of lives by making mosquitoes unable to transmit malaria or by eliminating the insects entirely. The possibility of a definitive solution to major infectious diseases makes a compelling case for a such a techno fix.
Researchers Create New System for Safer Gene-Drive Testing and Development
24471M. Aguilera, UC San Diego Today, 2023-01-12 08:46:16.
In the journal Nature Communications, University of California San Diego researchers led by former Postdoctoral Scholar Gerard Terradas together with Postdoctoral Scholar Zhiqian Li and Professor Ethan Bier, in close collaboration with UC Berkeley graduate student Jared Bennett and Associate Professor John Marshall, describe the development of a new system for testing and developing gene drives in the laboratory and safely converting them into tools for potential real-world applications. “These studies both empower new engineering of gene-drive systems while providing important information regarding how to assess and analyze key interactions between their most important moving parts,” said Bier, a faculty member in the School of Biological Sciences, Department of Cell and Developmental Biology. CRISPR-based gene drives feature a protein called a Cas9 endonuclease and a guide RNA molecule that join forces to direct DNA cuts to specific sites in the genome where new genetic elements can be inserted. As the DNA repairs these cuts, the new genetic elements are copied from one chromosome to another, resulting in offspring that exceed the standard 50-50 percent inheritance, instead favoring the newly inserted genetic elements.
Environmental, Socio-economic, and Health Impact Assessment (ESHIA) for Gene Drive Organisms
24428isaaa Inc. and Outreach Network for Gene Drive Research, ISAAA, 2023-01-11 10:31:02.
Understanding the possible positive and negative impacts that gene drive organisms could have on the environment and people is essential before these technologies are considered for release, whether for research purposes or for use. Different impacts are assessed through different tools and methodologies. While environmental risks are evaluated through specific risk assessments, other dimensions, such as positive and negative impacts on a social, economic, and health level can be assessed through impact assessments. These environmental, socio-economic and health impact assessments can complement the information provided by environmental risk assessments.
Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives
24363J. Chen, X. Xu and J. Champer, bioRxiv, 2023.01.06.522951. 2023-01-06 09:33:07.
New types of gene drives promise to provide increased flexibility, offering many options for confined modification or suppression of target populations. Among the most promising are CRISPR toxin-antidote gene drives, which disrupt essential wild-type genes by targeting them with Cas9/gRNA, resulting in their removal. This increases the frequency of the drive in the population. All these drives, plus homing modification rescue drives, rely on having an effective rescue element, which consists of a recoded version of the target gene. This rescue element can be at the same site as the target gene, which maximizes the chance of efficient rescue, or at a distant site, which allows some other useful options, such as easily disrupting another essential gene or achieving greater confinement. Previously, we developed a homing rescue drive targeting a haplolethal gene and a toxin-antidote drive targeting an essential but haplosufficient gene. These successful drives had functional rescue elements but suboptimal drive efficiency. Here, we attempted to construct new toxin-antidote drives targeting these genes with a distantsite configuration from three different loci. We found that use of additional gRNAs increased cut rates to nearly 100%. However, all distant-site rescue elements failed for both haplolethal and haplosufficient target genes. Furthermore, one rescue element with a minimally recoded rescue element was used as a template for homology-directed repair for the target gene on a different chromosomal arm, resulting in the formation of functional resistance alleles at high frequency. Together, these results can inform the design of future CRISPR-based toxin-antidote gene drives.Competing Interest StatementThe authors have declared no competing interest.
The Possibilities of Gene Drives for Managing Populations and Controlling Diseases
27641J. Vijay Upadhye, U. N. Shah and B. Mudhol, Salud, Ciencia y Tecnologia, 3. 2023-01-01 07:51:35.
The technical limitations and the use of gene drives to address ecological problems by modifying all populations of wild species remain primarily speculative. Here, we examine the possibility that RNA-guided gene drives based on the CRISPR nuclease Cas9 could be used as an all-encompassing approach for introducing changed features into natural populations over a long period. We outline potential capabilities and possible disadvantages and offer new preventative measures to stem from the propagation of genes and undo genetic modifications. Editing the sexual animal population would significantly benefit both people and the environment. For instance, RNA-guided gene drives may stop the spread of illness, assist farming by correcting bug and weed chemicals and resistance to herbicides, and manage harmful invasive species. However, each prospective use needs to be carefully evaluated due to the likelihood of unfavorable ecological repercussions and the near inevitability of dissemination beyond political boundaries. To investigate the responsible application of this now hypothetical technology, we want serious, inclusive, educated public conversations. © 2023; Los autores.
CRISPR Gene Drives: A Weapon of Mass Destruction?
24336J. Ng, Medium, 2022-12-29 08:40:22.
Gene drives allow scientists to “drive” new genes — and their associated traits — into wildlife populations at unprecedented rates. Here’s a simplified explanation of how gene drives work. In normal sexual reproduction between species with two copies of chromosomes, each gene has a 50% chance of being inherited. However, there are particular DNA sequences called “selfish genes” whose frequency in the genome increases with each generation, even if this doesn’t result in an evolutionary advantage for the offspring. In 2003, biologist Austin Burt proposed a new way to use selfish genes to spread traits more efficiently through a population and ensure that offspring have a 100% probability of inheriting a particular DNA segment.
Gene drive designs for efficient and localisable population suppression using Y-linked editors
24339R. Geci, K. Willis and A. Burt, PLOS Genetics, 18:e1010550. 2022-12-27 08:45:03.
Author summary Some pest populations can be successfully controlled by the inundative release of sterile males, but this approach is not practicable when the target population is large or the species difficult to rear. Computer modelling has previously demonstrated that releasing males with a genomic editor on their Y chromosome that kills or sterilises female descendants could be much more efficient, particularly if combined with a sex ratio distorter. Here we extend this work to show that Y-linked editors can also be used in even more efficient gene drive designs that would spread over successive generations beyond the region of release. Such spread could nonetheless be controlled by exploiting relatively small pre-existing differences in gene frequency between populations to restrict the spread and impact of the constructs, if desired. The proposed design does not require high rates of recombinational repair of DNA breaks or expression off the Y chromosome during meiosis, potentially expanding the range of species in which such low release rate control is possible. Y-linked editors may therefore form the basis of a highly flexible set of genetic strategies for population control.
Use of Insect Promoters in Genetic Engineering to Control Mosquito-Borne Diseases
24584V. Bottino-Rojas and A. A. James, Biomolecules, 13. 2022-12-22 10:33:51.
Mosquito transgenesis and gene-drive technologies provide the basis for developing promising new tools for vector-borne disease prevention by either suppressing wild mosquito populations or reducing their capacity from transmitting pathogens. Many studies of the regulatory DNA and promoters of genes with robust sex-, tissue- and stage-specific expression profiles have supported the development of new tools and strategies that could bring mosquito-borne diseases under control. Although the list of regulatory elements available is significant, only a limited set of those can reliably drive spatial-temporal expression. Here, we review the advances in our ability to express beneficial and other genes in mosquitoes, and highlight the information needed for the development of new mosquito-control and anti-disease strategies.
Genetically modified mosquitoes … could CRISPR gene editing end malaria?
24315D. Wells, SelectScience, 2022-12-22 08:44:13.
Despite being a preventable and treatable disease, malaria is currently affecting the lives of more than 200 million people.1 This results in over half a million deaths per year, with 80% of this mortality occurring in children under the age of 5.2 In addition to the tragic social and humanitarian considerations, the economic losses to Africa attributed to malaria equate to around $12 billion a year.3 Hence, the public health burden of malaria is huge, and continued efforts in malaria control, elimination strategies, and case management are crucial to minimizing the devastation that malaria has on at-risk communities. In this article, we explore the innovative use of genetically modified mosquitoes as a means of fighting this devastating disease.
Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it
24281B. A. Hay and M. Guo, Proceedings of the National Academy of Sciences, 119:e2218020119. 2022-12-20 14:19:44.
How can the ability of t w2 to spread at super-Mendelian frequencies be utilized even if it is unable to directly drive the population to an unfit state? Gierus, Birand, and colleagues proposed placing Cas9 and a gRNA at a neutral position within the t haplotype. In this hybrid gene drive element, which they refer to as tCRISPR, Cas9 and the gRNA cleave and (hopefully) create loss-of-function (LOF) alleles in the male germ line of the prolactin (Prl) gene, which is required for female fertility. The goal with tCRISPR is for t-based segregation distortion in males to pump the Cas9/gRNAs cassette to high frequency within the population. The latter, through cleavage followed by inaccurate repair in males, will continuously produce LOF alleles at the independently segregating Prl locus. The hope is that the combination of t-based drive and accumulation of Prl LOF alleles will drive the population to an unfit state that contains a high frequency of infertile homozygous Prl mutant females along with some frequency of infertile homozygous t males. The combination of these two effects, they propose, could eliminate populations under a wider range of parameters than with t w2 alone
Gene editing and agrifood systems
24291FAO, FAO, 2022-12-20 09:22:56.
Gene-editing technologies represent a promising new tool for plant and animal breeding in low- and middle-income countries. They enhance precision and efficiency over current breeding methods and could lead to rapid development of improved plant varieties and animal breeds. However, as for any new technology, they have their merits and demerits. There is, as yet, no international consensus regarding if and how gene-edited organisms should be regulated, and whether their release would fall under the regulatory framework of the Cartagena Protocol on Biosafety to the Convention on Biological Diversity. This science- and evidence-based Issue Paper on gene editing and agrifood systems presents a balanced discussion of the most pertinent aspects of gene editing, including the consequences for human hunger, human health, food safety, effects on the environment, animal welfare, socioeconomic impact and distribution of benefits. Intrinsic ethical concerns and issues of governance and regulation are addressed, and the roles of the public and private sectors, alone and in partnership, are summarized. Various scenarios are also presented for how gene editing might be used in the future to help transform agrifood systems.
Exploring the value of a global gene drive project registry
24279R. I. Taitingfong, C. Triplett, V. N. Vásquez, R. M. Rajagopalan, R. Raban, A. Roberts, G. Terradas, B. Baumgartner, C. Emerson, F. Gould, F. Okumu, C. E. Schairer, H. C. Bossin, L. Buchman, K. J. Campbell, A. Clark, J. Delborne, K. Esvelt, J. Fisher, R., Nature Biotechnology, 2022-12-15 14:15:40.
Recent calls to establish a global project registry before releasing any gene-drive-modified organisms (GDOs) have suggested a registry could be valuable to coordinate research, collect data to monitor and evaluate potential ecological impacts, and facilitate transparent communication with community stakeholders and the general public. Here, we report the results of a multidisciplinary expert workshop on GDO registries convened on 8–9 December 2020 involving 70 participants from 14 countries. Participants had expertise in gene drive design, conservation and population modeling, social science, stakeholder engagement, governance and regulation, international policy, and vector control; they represented 45 organizations, spanning national and local governmental agencies, international organizations, nonprofit organizations, universities, and district offices overseeing local vector control. The workshop aimed to gather perspectives on a central question: “In what ways could a gene-drive project registry both contribute to and detract from the fair development, testing and use of GDOs?” We specifically queried the perceived purpose of a registry, the information that would need to be included, and the perceived value of a registry. Three primary findings emerged from the discussion: first, many participants agreed a registry could serve a coordinating function for multidisciplinary and multisector work activities; second, doing so may require different design elements, depending on the target end-user group and intended purpose for that group; and third, these different information requirements lead to concerns about information sharing via a registry, suggesting potential obstacles to achieving transparency through such a mechanism. We conclude that any development of a gene-drive project registry requires careful and inclusive deliberation, including with potential end-users, to ensure that registry design is optimal.
Performance characteristics allow for confinement of a CRISPR toxin-antidote gene drive designed for population suppression
24272S. Zhang and J. Champer, bioRxiv, 2022.12.13.520356. 2022-12-15 14:08:18.
Gene drives alleles that can bias their own inheritance are a promising way to engineer populations for control of disease vectors, invasive species, and agricultural pests. Recent advancements in the field have yielded successful examples of powerful suppression type drives and confined modification type drives, but developing confined suppression drives has proven more difficult. This is because the necessary power for strong suppression is often incompatible with the characteristics needed for drive confinement. However, one type of CRISPR toxin-antidote drive may be strong enough and confined, the TADE (Toxin-Antidote Dominant Embryo) suppression drive. By disrupting a haplolethal target gene and a haplosufficient female fertility gene, this drive quickly eliminates wild-type alleles and eventually induces population suppression. It has been shown to perform effectively in panmictic populations. However, confinement in spatial scenarios may be substantially different. Here, we use a reaction-diffusion model to assess the performance of TADE suppression drive in continuous space. We measure the drive wave advance speed while varying several performance parameters and find that moderate fitness costs or embryo cutting (from maternally deposited nuclease) can eliminate the drive’s ability to form a wave of advance. We assess the release size required for the drive to propagate, and finally, we investigate migration corridor scenarios. Depending on the corridor size and dispersal, it is often possible for the drive to suppress one population and then persist in the corridor without invading the second population. This prevents re-invasion by wild-type, which may be a particularly desirable outcome in some scenarios. Thus, even imperfect variants of TADE suppression drive may be excellent candidates for confined population suppression.Competing Interest StatementThe authors have declared no competing interest.
New CRISPR tech makes it possible to wipe out invasive mice
241812022-12-11 11:12:20.
Experts urge caution over biotech that can wipe out insect pests
24153L. Fauvel, Phys Org, 2022-12-09 07:09:45.
Dozens of scientists, experts and campaigners called for a ban on the release of genetically-edited organisms into the wild, in a statement Friday warning of potentially severe risks to the world's pollinators. The appeal was launched at crunch biodiversity talks in Montreal, where delegates from almost all the world's countries were meeting to negotiate a strategy to halt human environmental destruction, which threatens the natural life support systems of the planet. A host of new genome-editing tools that modify the genetic material of living beings have emerged in recent years, and are being researched and developed largely to target insects and plants in agriculture. Supporters argue that they could help human health, agriculture and even species conservation. But their use in the wild carries "understudied risks which could accelerate the decline of pollinator populations and put entire food webs at risk," according to the letter drafted by the French non-governmental organization Pollinis.
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control the human malaria mosquito vector Anopheles gambiae
24161A. Qureshi and J. B. Connolly, Malaria Journal, 2022-12-06 07:52:06.
Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (i) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity. Amino acid sequences of hCas9 and DsRed were interrogated against those of toxins or allergens from NCBI, UniProt, COMPARE and AllergenOnline bioinformatic databases and the gRNA was compared with microRNAs from the miRBase database for potential impacts on gene expression associated with toxicity or allergenicity. PubMed was also searched for any evidence of toxicity or allergenicity of Cas9 or DsRed, or of the donor organisms from which these products were originally derive While Cas9 nuclease activity can be toxic to some cell types in vitro and hCas9 was found to share homology with the prokaryotic toxin VapC, there was no evidence of a risk of toxicity to humans and other animals from hCas9. Although hCas9 did contain an 8-mer epitope found in the latex allergen Hev b 9, the full amino acid sequence of hCas9 was not homologous to any known allergens. Combined with a lack of evidence in the literature of Cas9 allergenicity, this indicated negligible risk to humans of allergenicity from hCas9. No matches were found between the gRNA and microRNAs from either Anopheles or humans. Moreover, potential exposure to dsxFCRISPRh transgenic proteins from environmental releases was assessed as negligible.Bioinformatic and literature assessments found no convincing evidence to suggest that transgenic products expressed from dsxFCRISPRh were allergens or toxins, indicating that environmental releases of this population suppression gene drive for malaria vector control should not result in any increased allergenicity or toxicity in humans or animals. These results should also inform evaluations of other GMMs being developed for vector control and in vivo clinical applications of CRISPR-Cas9.
A natural gene drive could steer invasive rodents on islands to extinction
24129B. Brookshire, ScienceNews, 2022-12-05 09:12:58.
In the battle against the invasive house mouse on islands, scientists are using the rodent’s own genes against it. With the right tweaks, introducing a few hundred genetically altered mice could drive an island’s invasive mouse population to extinction in about 25 years, researchers report in the Nov. 15 Proceedings of the National Academy of Sciences. The trick is adding the changes to a section of mouse DNA that gets inherited far more often than it should. Scientists have been creating similar extra-inheritable genes — called gene drives — in the lab. The chunks are designed to get passed on to most or all of an animal’s offspring instead of the usual half, and make those offspring infertile in the bargain. Scientists have used gene drives to reduce populations of mosquitoes and fruit flies (SN: 12/17/18). But mammals are a different story. Scientists have previously synthesized a gene drive that gets passed on in mice about 80 percent of the time (SN: 1/23/19). But the drive isn’t strong enough to stop a population quickly. Luckily, nature has it handled. A haplotype is a naturally occurring group of genes that gets passed on as a unit during replication. The genome of the house mouse (Mus musculus) has a particular haplotype, called the t haplotype, that gets passed on to offspring more than 95 percent of the time, instead of the typical 50 percent.
East African policy dialogue on research of genetically modified mosquitoes for malaria control and elimination
24112C. Mugoya, Target Malaria, 2022-12-02 09:27:43.
The East African Community Secretariat, in collaboration with the East African Health Research Commission; NEPAD, AFIDEP and IFAKARA Health Institute recently convened an East African regional dialogue in Dar es salaam, Tanzania from 17-19 November 2022 to deliberate the way forward on the legal and regulatory frameworks guiding research on genetically modified mosquitoes to solve the problem of malaria in the East African region. The dialogue was attended by legislators from the seven countries of the East African Community partner states – Kenya, Uganda, Tanzania, Burundi, DR Congo, Rwanda and South Sudan, policy makers, government officials, and health experts including biotechnology/biosafety regulators.
Determining the landscape of resistance to gene drives in the malaria mosquito
27631I. Morianou, Imperial College London, 2022-12-01 10:17:51.
Gene drives are engineered selfish genetic elements with the potential to spread throughout entire insect populations for sustainable vector control. Recently, a gene drive was shown to eliminate caged populations of the malaria mosquito by targeting the highly conserved female-specific exon of the doublesex gene. This caused females, homozygous for the gene drive, to develop as sterile intersex individuals, leading to the observed population crash. However, target site resistant alleles that block gene drive activity, whilst encoding a functional copy of the target gene, may halt gene drive spread in the wild. These may be naturally occurring or generated by the gene drive itself. This thesis presents a pipeline for the discovery, genetic engineering, and testing of putative drive-resistant variants. First, to investigate the potential for natural resistance, existing population genomics data were interrogated for the presence of natural single nucleotide polymorphisms (SNPs) at the highly conserved gene drive target region. To investigate the potential for drive-induced resistance, a high-throughput assay was designed to generate a high volume of mutations at the gene drive target site and screen them for their ability to restore dsx function. These methods yielded three putatively resistant SNPs: one natural polymorphism and two rare Cas9-induced mutations. These were engineered in the mosquito genome for testing, using a novel method termed CRISPR-mediated cassette exchange (CriMCE). It was confirmed that all three polymorphisms are functional and offer full, partial or no resistance to gene drive. Importantly, partial resistance to gene drive is being demonstrated for the first time. To mitigate observed resistance, gene drive systems targeting multiple sites simultaneously were developed. These showed improved drive dynamics and caused rapid elimination of caged mosquito populations within 7-8 generations. The experimental pipeline described here can be applied to pre-empt and mitigate resistance against any gene drive strategy, prior to field testing.
Scientist Recommends Gene Drive Strategies Of Pest Control To Increase Food Security
24062L. Agbo, allnews, 2022-11-28 16:46:37.
A Nigerian scientist, Dr. Rose Gidado has recommended that Nigerian policymakers and farmers adopt the technology of a gene drive-based pest management technique in order to increase bumper harvest and food security.In an interview with NAN on Monday in Abuja, Gidado, the Deputy Director at the National Biotechnology Development Agency (NABDA) and the OFAB's Country Coordinator, made the statement.In order to attain food security, which would lead to national development, she claimed that Nigerian farmers needed to accept the use of gene drive technology for their seeds and food crops.“Gene drives are systems that warrant biased inheritance by improving the possibility of DNA sequence passing from one generation to the other via sexual reproduction and potentially throughout an entire population.“It is a modern biotechnology technique that alters the tendency of transmitting a specific allele from the natural 50 per cent probability by propagating a particular set of genes throughout a population,’’ Gidado said.
That new chestnut? USDA plans to allow the release of GE trees into wild forests
24060D. E. Davis, The Hill, 2022-11-27 16:42:48.
In the 21st century, there are those who believe the trees can be resuscitated via genetic engineering (GE). In fact, the U.S. Department of Agriculture (USDA) has just released a draft environmental impact statement and draft plant pest risk assessment that will allow the unrestricted planting of blight-tolerant GE chestnut trees on public and private lands. If approved, the tree would be the first genetically engineered plant released with the purpose of spreading freely into the wild. Although the agency is recommending the tree’s release into wild forests, they are also requesting public input regarding their recent decision to do so. (You can submit comments here.) The restoration of the American chestnut is a noble undertaking that certainly deserves our serious consideration and thoughtful deliberation. If the plan is accomplished successfully, the tree would improve forest health, increase biodiversity, and provide important economic benefits for local communities. However, as an environmental historian, I am deeply concerned that individuals endorsing the unregulated status of the GE chestnut have not sufficiently educated themselves about potential problems associated with genetically modified trees
Discovery of 119-Million-Year-Old “Selfish” Genes Casts Doubt on Established Evolution Beliefs
24042Stowers Institute for Medical Research, SciTechDaily, 2022-11-23 10:50:53.
Meiotic drivers, a kind of selfish gene, are indeed selfish. They are found in virtually all species’ genomes, including humans, and unjustly transfer their genetic material to more than half of their offspring, resulting in infertility and impaired organism health. Their longevity over evolutionary time was thought to be brief due to their parasitic potential, until recently. The Stowers Institute for Medical Research, in collaboration with the National Institute for Biological Sciences in Beijing, China, has discovered a selfish gene family that has survived for over 100 million years—ten times longer than any other meiotic driver ever identified—calling into question established beliefs about how natural selection and evolution deal with these threatening sequences.
Discovery of 119-Million year old Selfish Genes Casts Doubt on Established Evolution Beliefs
24039Stowers Institute for Medical Research, 2022-11-23 10:39:51.
Meiotic drivers, a kind of selfish gene, are indeed selfish. They are found in virtually all species’ genomes, including humans, and unjustly transfer their genetic material to more than half of their offspring, resulting in infertility and impaired organism health. Their longevity over evolutionary time was thought to be brief due to their parasitic potential, until recently. The Stowers Institute for Medical Research, in collaboration with the National Institute for Biological Sciences in Beijing, China, has discovered a selfish gene family that has survived for over 100 million years—ten times longer than any other meiotic driver ever identified—calling into question established beliefs about how natural selection and evolution deal with these threatening sequences.
Modeling-informed Engineered Genetic Incompatibility strategies to overcome resistance in the invasive Drosophila suzukii
28350A. Sychla, N. R. Feltman, W. D. Hutchison and M. J. Smanski, Frontiers in Insect Science, 2. 2022-11-22 10:46:03.
Engineered Genetic Incompatibility (EGI) is an engineered extreme underdominance genetic system wherein hybrid animals are not viable, functioning as a synthetic speciation event. There are several strategies in which EGI could be leveraged for genetic biocontrol of pest populations. We used an agent-based model of Drosophila suzukii (Spotted Wing Drosophila) to determine how EGI would fare with high rates of endemic genetic resistance alleles. We discovered a surprising failure mode wherein field-generated females convert an incompatible male release program into a population replacement gene drive. Local suppression could still be attained in two seasons by tailoring the release strategy to take advantage of this effect, or alternatively in one season by altering the genetic design of release agents. We show in this work that data from modeling can be utilized to recognize unexpected emergent phenomena and a priori inform genetic biocontrol treatment design to increase efficacy.
A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias
24021S. A. N. Verkuijl, E. Gonzalez, M. Li, J. X. D. Ang, N. P. Kandul, M. A. E. Anderson, O. S. Akbari, M. B. Bonsall and L. Alphey, Nature Communications, 13:7145. 2022-11-21 09:45:13.
CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Homing drives are designed to replace a wild-type allele with a copy of a drive element on the homologous chromosome. In Aedes aegypti, the sex-determining locus is closely linked to the white gene, which was previously used as a target for a homing drive element (wGDe). Here, through an analysis using this linkage we show that in males inheritance bias of wGDe did not occur by homing, rather through increased propagation of the donor drive element. We test the same wGDe drive element with transgenes expressing Cas9 with germline regulatory elements sds3, bgcn, and nup50. We only find inheritance bias through homing, even with the identical nup50-Cas9 transgene. We propose that DNA repair outcomes may be more context dependent than anticipated and that other previously reported homing drives may, in fact, bias their inheritance through other mechanisms.
Should we use a genetic weapon against mosquitoes carrying malaria?
23988T. H. Saey, ScienceNewsExplores, 2022-11-17 08:58:08.
In a large laboratory cage, a male mosquito carries a genetic weapon that could launch the destruction of his species. That loss could also mean the end of the parasite that causes malaria. The weapon? A self-replicating bit of DNA known as a gene drive. It’s one of the most anticipated tools being developed to stop mosquitoes from spreading diseases like malaria to humans. It’s also one of the most controversial. The gene drive interferes with the insects’ ability to reproduce. In one small lab study, it wiped out captive populations of mosquitoes in just eight to 12 generations. A larger study in outdoor cages in Terni, Italy, worked too. Within as little as five to 10 years, this gene drive could be ready to test in the wild. Researchers are eyeing Africa for the first test release. There, malaria takes a huge toll. In 2020, it sickened close to 241 million people on the continent. And most of the globe’s 670,000 malaria deaths that year were in Africa. About eight in every 10 were children, the World Health Organization says. Many tools have been made to fight the disease. There are preventive drugs, insecticide-treated bed nets and even vaccines. These efforts are helping. But mosquitoes are developing resistance to insecticides. And some anti-malaria drugs may no longer work well. “To go toward zero [cases], we need to have something that is transformational,” says Fredros Okumu. By that, he means a completely new type of strategy. Okumu is a mosquito biologist. He directs science programs at Ifakara Health Institute in Tanzania, a country in East Africa. Gene drives might be the big change people are looking for. This technology was first devised in 2015. Researchers are still refining and testing it. Other types of genetically altered mosquitoes have been released in Brazil, the United States and elsewhere. But so far, those altered genes spread slowly among wild populations. Gene drives could potentially spread to nearly every member of a species quickly. In this way, they could forever alter the species. Or even wipe it out.
The effect of mating complexity on gene drive dynamics
23967P. Verma, R. G. Reeves, S. Simon, M. Otto and C. S. Gokhale, The American Naturalist, 2022-11-15 12:33:47.
Gene drive technology promises to deliver on some of the global challenges humanity faces today in health care, agriculture, and conservation. However, there is a limited understanding of the consequences of releasing self-perpetuating transgenic organisms into wild populations under complex ecological conditions. In this study, we analyze the impact of three such complexities—mate choice, mating systems, and spatial mating network—on the population dynamics for two distinct classes of modification gene drive systems. All three factors had a high impact on the modeling outcome. First, we demonstrate that distortion-based gene drives appear to be more robust against mate choice than viability-based gene drives. Second, we find that gene drive spread is much faster for higher degrees of polygamy. Including a fitness cost, the drive is fastest for intermediate levels of polygamy. Finally, the spread of a gene drive is faster and more effective when the individuals have fewer connections in a spatial mating network. Our results highlight the need to include mating complexities when modeling the properties of gene drives, such as release thresholds, timescales, and population-level consequences. This inclusion will enable a more confident prediction of the dynamics of engineered gene drives and possibly even inform about the origin and evolution of natural gene drives.
CRISPR-Mediated Cassette Exchange (CriMCE): A Method to Introduce and Isolate Precise Marker-Less Edits
24026I. Morianou, A. Crisanti, T. Nolan and A. M. Hammond, The CRISPR Journal, 2022-11-15 09:33:31.
The introduction of small unmarked edits to the genome of insects is essential to study the molecular underpinnings of important biological traits, such as resistance to insecticides and genetic control strategies. Advances in CRISPR genome engineering have made this possible, but prohibitively laborious for most laboratories due to low rates of editing and the lack of a selectable marker. To facilitate the generation and isolation of precise marker-less edits we have developed a two-step method based on CRISPR-mediated cassette exchange (CriMCE) of a marked placeholder for a variant of interest. This strategy can be used to introduce a wider range of potential edits compared with previous approaches while consolidating the workflow. We present proof-of-principle that CriMCE is a powerful tool by engineering three single nucleotide polymorphism variants into the genome of Anopheles gambiae, with 5?41???higher rates of editing than homology-directed repair or prime editing.
Gene drive could be used to wipe out invasive mice on islands
23862M. Le Page, NewScientist, 2022-11-11 10:11:35.
For the first time, researchers have created a gene drive – a kind of genetic parasite – that could be used to eradicate mammalian pests such as mice by making them infertile. The technology could provide a humane alternative to the poison baits currently used to tackle invasive mice on islands, which have severe impacts on native birds, reptiles and plants. “It’s the first example of a mammalian gene drive technology that has had proof of concept in a laboratory setting,” says Paul Thomas at the University of Adelaide in Australia. Most animals have two copies of each chromosome, but their offspring gets only one copy from each parent. This means that if a piece of DNA is added to one chromosome of an individual, only half its offspring will inherit it. Gene drives are bits of DNA that encode various mechanisms for cheating the system and ensuring they get inherited by more than half of offspring. This means they can spread in a population even if they are harmful. Various kinds of natural gene drives have been discovered. In 2013, Kevin Esvelt at Massachusetts Institute of Technology created the first synthetic gene drive using the gene-editing technology CRISPR. Such CRISPR-based gene drives work extremely well in insects and several teams hope to use them to prevent the spread of malaria, either by wiping out mosquitoes or by making them less likely to infect people.
World first trial to eradicate mice through gene modification
23838I. Mannix, COSMOS, 2022-11-10 09:51:29.
Mouse populations could be eradicated in some areas through new gene modification technology to render female mice infertile. The technology – called t-CRISPR – was previously developed to target malaria-transmitting mosquitoes. This is the first proof of concept for its use as a mammalian genetic biocontrol tool targeting house mice, which is an invasive pest in Australia. In time, it could be used to control rodents on islands and landmasses where they cause widespread destruction. The research, published in Proceedings of the National Academy of Sciences, is the first time t-CRISPR has been successfully tested on mammals in a laboratory setting, according to senior author Professor Paul Thomas. Computer modelling conducted by the team suggests about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. “We have had mouse plagues in Australia for 150 years and existing controls, like baits, cause inhumane death and are expensive and labour intensive to deploy,” says Thomas, who works across the University of Adelaide and the South Australian Health and Medical Research Institute.
SHOULD WE CREATE GENE DRIVE GREY SQUIRRELS
23962S. Hartley and T. Law, GeneDriveGovernance.org, 2022-11-09 11:48:04.
UK scientists have proposed gene drive as a management tool to control grey squirrels. Now is a good time to talk about this emerging technology because the hopes and concerns of experts, stakeholders and the public can help to determine if or how it might be developed. To help foster this debate, we made a short research film on gene drive grey squirrels. The film draws on our social science research to show the complexity of the problem of grey squirrel control and invites you to think about whether scientists should develop gene drive squirrels or not.
Leveraging a natural murine meiotic drive to suppress invasive populations
23835L. Gierus, A. Birand, M. D. Bunting, G. I. Godahewa, S. G. Piltz, K. P. Oh, A. J. Piaggio, D. W. Threadgill, J. Godwin, O. Edwards, P. Cassey, J. V. Ross, T. A. A. Prowse and P. Q. Thomas, Proceedings of the National Academy of Sciences, 119:e2213308119. 2022-11-08 09:36:13.
Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (t(CRISPR)) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene (Prl). Using spatially explicit individual-based in silico modeling, we show that t(CRISPR) can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic t(CRISPR) mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.
WORLDWIDE: EXPERTS ON GENE DRIVES
23840Stop Gene Drive, STOP GENE DRIVES, 2022-11-07 09:51:54.
We are travelling the world speaking to some of the world’s leading thinkers, activists and academics on the impact of gene drives. We interviewed more than 20 experts from around the world
Making waves: Comparative analysis of gene drive spread characteristics in a continuous space model
23816M. Pan and J. Champer, bioRxiv, 2022.11.01.514650. 2022-11-02 10:23:47.
With their ability to rapidly increase in frequency, gene drives can be used to modify or suppress target populations after an initial release of drive-containing individuals. Recent advances in this field have revealed many possibilities for different types of drives, and several of these have been realized in experimental demonstrations. These drives all have unique advantages and disadvantages related to their ease of construction, confinement, and capacity to act as a modification or suppression system. While many properties of these drives have been explored in modelling studies, assessment of these drives in continuous space environments has been limited, often focusing on outcomes rather than fundamental properties. Here, we conduct a comparative analysis of many different gene drive types that have the capacity to form a wave of advance against wild-type alleles in one-dimensional continuous space. We evaluate the drive wave speed as a function of drive performance and ecological parameters, which reveals substantial differences between drive performance in panmictic versus spatial environments. In particular, we find that suppression drive waves are uniquely vulnerable to fitness costs and undesired CRISPR cleavage activity that can form resistance alleles in embryos by maternal deposition. Some drives, though, retain robust characteristics even with widely varying performance characteristics. To gain a better understanding of drive waves, we compare panmictic performance of drives across the full range of drive frequencies. We find that rates of wild-type allele removal in panmictic setting is correlated with drive wave speed, though this is also affected by a range of other factors. Overall, our results provide a useful resource for understanding the performance of drives in continuous spatial environments, which may be most representative of potential drive deployment in many relevant scenarios.Competing Interest StatementThe authors have declared no competing interest.
Modeling the efficacy of CRISPR gene drive for snail immunity on schistosomiasis control
23810R. E. Grewelle, J. Perez-Saez, J. Tycko, E. K. O. Namigai, C. G. Rickards and G. A. De Leo, PLOS Neglected Tropical Diseases, 16:e0010894. 2022-10-31 09:02:03.
CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. Gene drive technology in mollusks has received little attention despite the role of freshwater snails as hosts of parasitic flukes causing 200 million annual cases of schistosomiasis. A successful drive in snails must overcome self-fertilization, a common feature of host snails which could prevents a drive's spread. Here we developed a novel population genetic model accounting for snails' mixed mating and population dynamics, susceptibility to parasite infection regulated by multiple alleles, fitness differences between genotypes, and a range of drive characteristics. We integrated this model with an epidemiological model of schistosomiasis transmission to show that a snail population modification drive targeting immunity to infection can be hindered by a variety of biological and ecological factors; yet under a range of conditions, disease reduction achieved by chemotherapy treatment of the human population can be maintained with a drive. Alone a drive modifying snail immunity could achieve significant disease reduction in humans several years after release. These results indicate that gene drives, in coordination with existing public health measures, may become a useful tool to reduce schistosomiasis burden in selected transmission settings with effective CRISPR construct design and evaluation of the genetic and ecological landscape.
Pulled, pushed or failed: the demographic impact of a gene drive can change the nature of its spatial spread
23805L. Kläy, L. Girardin, V. Calvez and F. Débarre, arXiv, 2022-10-25 07:50:10.
Understanding the temporal spread of gene drive alleles -- alleles that bias their own transmission -- through modeling is essential before any field experiments. In this paper, we present a deterministic reaction-diffusion model describing the interplay between demographic and allelic dynamics, in a one-dimensional spatial context. We focused on the traveling wave solutions, and more specifically, on the speed of gene drive invasion (if successful). We considered various timings of gene conversion (in the zygote or in the germline) and different probabilities of gene conversion (instead of assuming 100% conversion as done in a previous work). We compared the types of propagation when the intrinsic growth rate of the population takes extreme values, either very large or very low. When it is infinitely large, the wave can be either successful or not, and, if successful, it can be either pulled or pushed, in agreement with previous studies (extended here to the case of partial conversion). In contrast, it cannot be pushed when the intrinsic growth rate is vanishing. In this case, analytical results are obtained through an insightful connection with an epidemiological SI model. We conducted extensive numerical simulations to bridge the gap between the two regimes of large and low growth rate. We conjecture that, if it is pulled in the two extreme regimes, then the wave is always pulled, and the wave speed is independent of the growth rate. This occurs for instance when the fitness cost is small enough, or when there is stable coexistence of the drive and the wild-type in the population after successful drive invasion. Our model helps delineate the conditions under which demographic dynamics can affect the spread of a gene drive.
What are gene drivers and why do 300,000 people want them banned?
23828Anika, Social Bites, 2022-10-21 23:39:53.
Ecologists in Action and Madrid Agroecologico submitted 300,000 citizen signatures to the Ministry of Ecological Transition and Demographic Challenge, asking Minister Teresa Ribera to give Spain a boost. International moratorium on technology for the release of organisms modified with gene drives (OIG) It will be discussed during the negotiations of the XV Conference on the Convention on Biological Diversity to be held in December. During the delivery of the signatures, the participants risks to human health and the environment of this new gene technology. Activists claimed with a banner that this genetic engineering technology contained an international moratorium and “danger” for environmentalists.
Target Malaria’s scientists are working to rid Africa of an ancient plague
23783D. Matthews, Vox, 2022-10-20 07:12:04.
This could very well be the last century in human history when people die from malaria. If and when we do eradicate the disease, the team at Target Malaria will probably deserve a big share of the credit. Their plan to use gene drive technology to wipe out species of mosquitoes carrying the parasitic illness represents the most promising path to eradicating a disease that killed on the order of 150 million to 300 million people over the 20th century, and still kills hundreds of thousands each year. Malaria used to be broadly common across most of the populated world, covering much of North America, Europe, Japan, and Australia, in addition to its current locations in Africa, Latin America, and South Asia. As the researchers Max Roser and Hannah Ritchie note, “poet Friedrich Schiller contracted the disease in Mannheim, Oliver Cromwell in Ireland, and Abraham Lincoln in Illinois.” Malaria no longer exists in those areas due to decades of public health measures like the drainage of mosquito breeding sites and use of pesticides like DDT, as well as economic development that gave residents resources to prevent and treat the disease.
Hurdles in responsive community engagement for the development of environmental biotechnologies
25089A. M. Normandin, L. M. Fitzgerald, J. Yip and S. W. Evans, Synthetic Biology, 7:ysac022. 2022-10-20 06:56:55.
Recent calls for engaging communities in biotechnology development do not draw enough attention to the hurdles that must be overcome for engagement strategies to effectively feed back into research design and conduct. These hurdles call into question many standard ways of operating and assessing in traditional scientific disciplines. The first steps in addressing these hurdles can be the most difficult. In reflecting on our own experiences in the early-stage development of environmental biotechnologies, we provide a set of techniques to help scientists and their collaborators learn to become more responsive to the needs and attitudes of communities with which they are engaging.Graphical Abstract
Driving down malaria transmission with engineered gene drives
23780W. T. Garrood, P. Cuber, K. Willis, F. Bernardini, N. M. Page and R. E. Haghighat-Khah, Frontiers in Genetics, 13. 2022-10-19 07:08:43.
The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female Anopheles mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs. The utility of genetically engineered gene drive mosquitoes as tools to decrease the burden of malaria by controlling the disease-transmitting mosquitoes is being evaluated. To date, there has been remarkable progress in the development of CRISPR/Cas9-based homing endonuclease designs in malaria mosquitoes due to successful proof-of-principle and multigenerational experiments. In this review, we examine the lessons learnt from the development of current CRISPR/Cas9-based homing endonuclease gene drives, providing a framework for the development of gene drive systems for the targeted control of wild malaria-transmitting mosquito populations that overcome challenges such as with evolving drive-resistance. We also discuss the additional substantial works required to progress the development of gene drive systems from scientific discovery to further study and subsequent field application in endemic settings.
Why we need to talk about ‘gene-drive’ grey squirrels
23778Anonymous, University of Exeter, 2022-10-17 07:04:37.
Would the best way of controlling the UK’s rampant grey squirrel population be to spread genetic changes throughout the species? A new research film, to be shown next month at Exeter Phoenix, sees scientists, conservation and wildlife experts debate the use of emergent ‘gene-drive’ technology in grey squirrels. The film Should we create gene drive grey squirrels?, written and produced by Sarah Hartley, a Professor in Technology Governance at the University of Exeter Business School, and independent film-maker Tom Law, documents the introduction into the UK of grey squirrels at the turn of the 20th Century and how their burgeoning population has contributed to the demise of the UK’s native red squirrel, which is now mainly found in Scotland. It presents the reasons why some people argue it would be better to limit the grey squirrel population, including the fact that they carry and spread squirrel pox, a virus fatal to red squirrels which can devastate entire populations.
Mosquito Gene Drives and the Malaria Eradication Agenda
23731Editor: R. Carballar-Lejarazu,, Jenny Stanford Publishing, 2022-10-17 06:37:46.
Malaria is one of most serious infectious diseases today and has afflicted humankind for thousands of years. A significant number of people still die from this mosquito-borne disease, despite the use of various malaria prevention and control methods over hundreds of years and more than a century of coordinated global control efforts using modern tools, together with research into and development of new strategies for prevention, diagnosis, and disease treatment. Genetic approaches that focus on the vector mosquitoes to prevent malaria parasite transmission have been considered for many decades. Genetic control strategies received a significant boost with the successful development of gene-drive systems, genetic methods for rapidly spreading beneficial genes and phenotypes through mosquito populations. This book reviews some concepts of gene drive systems and describes pioneering applications to control mosquito populations and prevent parasite transmission.
Assessing single-locus CRISPR/Cas9-based gene drive variants in the mosquito Aedes aegypti via single generation crosses and modeling
23756W. Reid, A. E. Williams, I. Sanchez-Vargas, J. Lin, R. Juncu, K. E. Olson and A. W. E. Franz, G3 Genes|Genomes|Genetics, 2022-10-17 06:25:18.
Critical to the design of a single-locus autonomous GD is that the selected genomic locus is amenable to both GD and appropriate expression of the antiviral effector. In our study, we used reverse engineering to target two intergenic genomic loci, which had previously shown to be highly permissive for antiviral effector gene expression, and we further investigated the use of three promoters (nanos, β2-tubulin, or zpg) for Cas9 expression. We then quantified the accrual of insertions or deletions (indels) after single generation crossings, measured maternal effects, and assessed fitness costs associated with the various transgenic lines to model the rate of GD fixation. Overall, MGDrivE modeling suggested that when an autonomous GD is placed into an intergenic locus, the GD system will eventually be blocked by the accrual of GD blocking resistance alleles and ultimately be lost in the population. Moreover, while genomic locus and promoter selection were critically important for the initial establishment of the autonomous GD, it was the fitness of the GD line that most strongly influenced the persistence of the GD in the simulated population. As such, we propose that when autonomous CRISPR/Cas9 based GD systems are anchored in an intergenic locus, they temporarily result in a strong population replacement effect, but as GD-blocking indels accrue, the GD becomes exhausted due to the fixation of CRISPR resistance alleles.
Introgression of a synthetic sex ratio distortion transgene into different genetic backgrounds of Anopheles coluzzii
23760P. Pollegioni, T. Persampieri, R. L. Minuz, A. Bucci, A. Trusso, S. Di Martino, C. Leo, M. Bruttini, M. Ciolfi, A. M. Waldvogel, F. Tripet, A. Simoni, A. Crisanti and R. Müller, Insect Molecular Biology, 2022-10-17 06:14:10.
The development of genetically modified mosquitoes (GMM) and their subsequent field release offers innovative approaches for vector control of malaria. A non-gene drive self-limiting male-bias Ag(PMB)1 strain has been developed in a 47-year-old laboratory G3 strain of Anopheles gambiae s.l. When Ag(PMB)1 males are crossed to wild-type females, expression of the endonuclease I-PpoI during spermatogenesis causes the meiotic cleavage of the X chromosome in sperm cells, leading to fertile offspring with a 95% male bias. However, WHO states that the functionality of the transgene could differ when inserted in different genetic backgrounds of An. coluzzii which is currently a predominant species in several West-African countries and thus a likely recipient for a potential release of self-limiting GMMs. In this study, we introgressed the transgene from the donor Ag(PMB)1 by six serial backcrosses into two recipient colonies of An. coluzzii that had been isolated in Mali and Burkina Faso. Scans of informative SNP markers and whole-genome sequencing analysis revealed a nearly complete introgression of chromosome 3 and X, but a remarkable genomic divergence in a large region of the chromosome 2 between the later backcrossed (BC6) transgenic offspring and the recipient paternal strains. These findings suggested to extend the backcrossing breeding strategy beyond BC6 generation and increase the introgression efficiency of critical regions that have ecological and epidemiological implications through the targeted selection of specific markers. Disregarding of differential introgression efficiency, we concluded that the phenotype of the sex ratio distorter is stabile in the BC6 introgressed An. coluzzii strains. This article is protected by copyright. All rights reserved.
Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure
23734S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer, eLife, 11:e79121. 2022-10-14 06:37:55.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter driving CRISPR/Cas9, was able to eliminate a cage population of mosquitoes. A second version, purportedly improved upon the first by incorporating an X-shredder element (which biases inheritance towards male offspring), was similarly successful. Here, we analyze experimental data from each of these gene drives to extract their characteristics and performance parameters and compare these to previous interpretations of their experimental performance. We assess each suppression drive within an individual-based simulation framework that models mosquito population dynamics in continuous space. We find that the combined homing/X-shredder drive is actually less effective at population suppression within the context of our mosquito population model. In particular, the combined drive often fails to completely suppress the population, instead resulting in an unstable equilibrium between drive and wild-type alleles. By contrast, otherwise similar drives based on the nos promoter may prove to be more promising candidates for future development than originally thought.
GeneConvene Global Collaborative | Laboratory Containment of Arthropods Capable of Gene Drive: Best Practices and Recommendations
23739Hector Quemada, GeneConvene Global Collaborative, 2022-10-13 14:19:28.
This webinar is presented by members of the American Society of Tropical Medicine and Hygiene's American Committee of Medical Entomologists who were involved in drafting a recent Addendum to the ASTMH's Arthropod Containment Guidelines that specifically consider arthropods with gene drive systems. https://www.liebertpub.com/doi/10.1089/vbz.2021.0035
Combating Mosquito-Borne Diseases with CRISPR
23701N. Spahich, The Scientist, 2022-10-11 08:06:34.
Female mosquitoes are some of the deadliest organisms in the world due to their ability to spread infectious diseases through a simple bite. Mosquito-borne diseases such as yellow fever, Zika, Dengue fever, and malaria kill millions of humans every year, and there are limited therapeutics for their prevention and treatment. While in college, Omar Akbari worked as a public service intern testing the local mosquito population for human pathogens and eradicating these insects with chemicals. During this experience, he felt dissatisfied with the insecticide-based method of controlling mosquito population and wanted to find a better way to tackle the problem of mosquito-borne disease spread. With a multidisciplinary team in his laboratory at the University of California, San Diego, he now develops tools through genetic engineering techniques such as CRISPR to solve the world’s insect control problems.
Improvement of Resistance in Plants Against Insect-Pests Using Genome Editing Tools
25205S. Bhat and S. Kumar, Genome Editing: Current Technology Advances and Applications for Crop Improvement, 2022-10-09 09:31:41.
During growth period plants are subjected to both biotic and abiotic stresses. Like other biotic stresses, insect-pests are the most serious challenge for the plants particularly in yield losses. Genome editing techniques are becoming an emerging technology bringing real revolution in genetic engineering and biotechnology. Editing of targeted gene provides ways to elucidate extensive ranges of aims for the improvement, protection, and increased yield of various crops. Researchers all over the world have unraveled the usage of numerous gene editing methods from endonuclease to CRISPR/Cas in various aspects of plants like plant growth and development, insect-pest control, and other biotic stresses. The key goal of this chapter is to highlight various techniques of genome editing approaches which can be used to develop resistance in plants against insect-pests. New crop-based methods that reiterate the effective utilization of these techniques in insect-pest management as well as plant in resistance against pests are highlighted. This chapter also highlights the implication of genome editing as well as framework for its specific regulation.
Research: Scientists Modify Mosquitoes That Can’t Spread Malaria
23775N. Kharbanda, Onlymyhealth, 2022-10-07 07:00:18.
According to a research, scientists have found a way to genetically engineer mosquitoes with the capability to slow down the multiplication of malaria-causing parasites in their gut. This is an advance study, that can help in preventing the infecting of the disease in humans. The disease spreads in people because of a female mosquito when it bites someone infected with the malaria parasite. The parasite grows into the next stage in the mosquito’s gut and transports to its salivary glands, to infect the next human it bites. These modified mosquitoes produce compounds which interfere in the growth of malaria-causing parasites, which are then not able to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects are dead. The team of researchers from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation have created a model which can analyse the effect of such changes if used in various African settings. They also found that the modification of these mosquitoes could be helpful even in locations where the transmission rate is high.
Explained: How Scientists Are Genetically modifying Mosquitoes To Reduce Malaria
23772Anonymous, Outlook, 2022-10-07 06:57:17.
he Delhi High Court on Friday asked the state government to inform it within two weeks of the proposal of increasing the fine amount in mosquito breeding cases. The court last year took suo moto cognizance of the issue of large-scale mosquito breeding in the city, resulting in the spread of vector-borne diseases With a sudden increase in malaria cases across the country, a recent research might provide some respite. Scientists have genetically modified mosquitoes to slow the growth of malaria-causing parasites in their guts — an advancement that can help prevent transmission of the disease to humans. Though only around 10 per cent of mosquitoes live long enough for the infectious parasite to develop, malaria remains one of the most devastating diseases globally, putting at risk about half of the world’s population. In 2021, it infected 241 million people and killed 627,000 people.
Explained: How scientists engineered mosquitoes that cannot spread malaria
23670FP Explainers, Firstpost, 2022-10-06 08:14:50.
The world of science is reaching new heights. Scientists have now developed mosquitoes that will bite you but not cause malaria. The study was conducted by a team of researchers called Transmission: Zero at the Imperial College of London. The results of the research were published in the Science Advances journal. Genetically modified mosquitoes have the ability to slow the growth of malaria-causing parasites in their gut, an innovation that can help prevent transmission of the disease to humans. Owing to the devastating effects of Malaria, which is putting about half of the world’s population at risk, scientists came up with this new method in the hope to deter the growth of the parasite.
Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development
23648W. K. Tonui, V. Ahuja, C. J. Beech, J. B. Connolly, B. Dass, D. C. M. Glandorf, et al., Transgenic Research, 31:607. 2022-10-04 08:24:50.
Novel genetically modified biological control products (referred to as “GM biocontrol products”) are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.
Malaria Gene Drives: A Battle Of Wit Between The Government And Stakeholders
23650O. Onwumere, The Nigerian Voice, 2022-10-03 08:29:30.
Through the National Biosafety Management Agency (NBMA), guidelines for gene editing, primarily in agriculture, were approved by the Nigerian Federal Government in December 2020. As the first country in Africa, the government was praised for taking the momentous step of establishing guidelines for gene editing. The government sees science and technology as major drivers of agricultural productivity, as stated in the approved guidelines. This is due to the fact that the technology is guaranteed to be safe and won't harm the environment or human health. Scientists and non-governmental organizations have nonetheless refused to support the use of genetically engineered bacteria to eradicate malaria-carrying mosquitoes despite the government's actions. The reason was that a doctor from Nigeria who didn't want his name published said that gene-editing technology needs to be looked at carefully because there have been failed reports in some African countries, like Burkina Faso, where modified mosquitoes were released and people got bit by them
Malaria-free mosquito engineered by scientists
23697GNA, MODERN GHANA, 2022-10-03 07:54:35.
Scientists have genetically modified the main malaria-carrying species of mosquito in sub-SaharanAfrica to slow the growth of malaria-causing parasites in their gut, preventing transmission of thedisease to humans. When the Anopheles gambiae takes a blood meal, it produces two molecules called antimicrobialpeptides in its guts, according to the scientists. These peptides, which were originally isolated from honeybees and African clawed frogs, impair themalaria parasite's development. Now researchers from the Transmission Zero team at Imperial College London have come up with adesign that can be combined with existing “gene drive” technology to spread the modification anddrastically cut malaria transmission. Collaborators from the Institute for Disease Modelling at the Bill and Melinda Gates Foundation,which funded the research, also developed a model that, for the first time, can assess the impact ofsuch modifications if used in a variety of African settings. They found that the modification developed by the Imperial team could be a powerful tool forbringing down cases of malaria even where transmission is high.
Gene drive used to make all female mosquitoes sterile
23653Akfire1, TechiLink, 2022-10-01 08:45:17.
We have long known that we can limit malaria infections by controlling the mosquitoes that transmit them. But that knowledge has not translated into auditing efforts that have always been completely successful. Many of the approaches we have used to control mosquitoes have caused environmental problems, and mosquito populations are large enough that they have developed resistance to many of our pesticides. That made the development of so-called ‘gene drive’ constructs exciting (albeit a little scary). They have the potential to quickly spread genes across a population, including a mosquito population. But the prospect of modern genetic control of mosquito populations faces the very old problem of evolution, as gene drives often grind to a halt due to genetic changes that allow mosquito populations to escape their impact. Now a team has come up with a way to potentially avoid this problem: use gene drive to target a gene fundamental to mosquito development as male or female. By doing so, the females become sterile and, at least in the lab, the mosquito populations collapse.
Justifying an Intentional Species Extinction: The Case of Anopheles gambiae
23662D. E. Callies and Y. Rohwer, Environmental Values, 31:193-210. 2022-10-01 06:16:34.
Each year, over 200 million people are infected with the malaria parasite, nearly half a million of whom succumb to the disease. Emerging genetic technologies could, in theory, eliminate the burden of malaria throughout the world by intentionally eradicating the mosquitoes that transmit the disease. In this paper, we offer an ethical examination of the intentional eradication of Anopheles gambiae, the main malaria vector of sub-Saharan Africa. In our evaluation, we focus on two main considerations: the benefit of alleviating the malaria burden, and the loss of value that would accompany the eradication of the species. We outline a typology of the different ways in which species are valued or could be valuable, then use that typology to appraise the value of the species in question. We argue that Anopheles gambiae has minor (and redundant) instrumental value, little final subjective value and no objective final value.
How We’re Reducing Disease With Genetically Modified Mosquitoes
23667V. Wise, HealthMatch, 2022-09-29 08:07:21.
We all know mosquitoes as those annoying insects we swat away from our faces. They carry diseases, so we don’t want them anywhere near us. There are over 200 types of wild mosquitoes bugging us across America and the U.S. territories. Approximately 12 types can spread disease, but most are “nuisance” mosquitoes, which don’t spread germs. Obviously, it’s hard to identify a tiny flying creature, so we need to keep them all away from us just in case. Aedes aegypti¹ is one of the most common mosquitoes in the U.S. that can spread disease. One of the best-known mosquito-borne diseases is malaria, but Aedes aegypti is associated with 54 viruses². West Nile virus, Zika, and dengue are just three diseases these mosquitoes transmit around the U.S With 1 in 150 people becoming seriously ill due to West Nile virus, sometimes fatally, what can we do to prevent mosquito bites?
Scientists stunt parasite growth to tackle malaria
23769RSS24.news, RSS24.NEWS, 2022-09-29 06:52:01.
Loss of life, loss of livlihoods and homelessness have already afflicted these flood marooned refugees in Pakistan. Now these living conditions means they also face sickness and and without protection malaria is a major threat. Health agencies try to protect people against infection with sprays, nets and a vaccine for children, there are also preventative medicines. But despite all these, there were 241 million cases of malaria in 2020 and an estimated 627,000 deaths according to the latest malaria report from the World Health Organization (WHO). The WHO says these strategies, which are also used for other mosquito borne diseases such as Zika and dengue, are only partially effective. In the meantime the insects are becoming inceasingly resistant to insecticides. Scientists have for many years been investigating whether they can control the life cycle of mosquitoes by manipulating their DNA, thereby creating genetically modified mosquitoes. The disease is spread by a parasite Plasmodium falciparum which grows and reaches maturation inside the female Anopheles mosquito.
Scientists are manipulating the DNA of mosquitoes to fight the spread of malaria
23766R. Min, EURONEWS.NEXT, 2022-09-29 06:48:00.
Scientists say they have managed to genetically modify mosquitoes so that they are unable to spread malaria, a disease that kills well over half a million people each year. The changes cause mosquitoes to live shorter lives, while the parasites inside them, which cause the fatal infection, develop more slowly. This slashes the chances of mosquitoes living long enough to carry fully grown parasites – and transmit the disease to the humans they bite.Malaria is spread by the parasite Plasmodium falciparum, which grows and reaches maturation inside the female Anopheles mosquito. The average mosquito survives on average seven to 10 days in the wild. "By prolonging the developmental time that the parasite needs inside the mosquito to become infectious, this 10 per cent becomes now much smaller".
Scientists engineer mosquitoes that cannot spread malaria
23601J. Dalton, Independen, 2022-09-22 14:30:39.
Scientists have engineered mosquitoes that cannot give humans malaria, saying their work could potentially eliminate the disease. Researchers at Imperial College London genetically modified the insects so that the growth of malaria-causing parasites in their guts was slowed.
Scientists Engineer Mosquitoes That Can’t Transmit Malaria
23598C. Murez, US News, 2022-09-22 14:21:57.
The fight against malaria could hinge on genetically engineered mosquitoes that have something called "gene drive."Researchers from the Transmission: Zero team at Imperial College London report that they have engineered mosquitoes that slow the growth in their gut of the parasites that cause malaria. This delay would mean the mosquito would reach its natural life span before the parasite would reach the mosquitoes' salivary glands. So a bite wouldn't spread the disease. In the lab, this dramatically reduced the spread of malaria. "Since 2015, the progress in tackling malaria has stalled. Mosquitoes and the parasites they carry are becoming resistant to available interventions such as insecticides and treatments, and funding has plateaued. We need to develop innovative new tools," study co-author Tibebu Habtewold said in a college news release. He's a researcher from the college's Department of Life Sciences. Last year, malaria infected 241 million people, killing 627,000 of them, mostly children younger than age 5 in sub-Saharan Africa.
Mosquitoes that can’t spread malaria engineered by scientists
235842022-09-22 14:04:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing 'gene drive' technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Scientists engineer mosquitoes that can’t spread malaria
23581S. Varshney, Gamacher Central, 2022-09-22 13:58:18.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.
Mosquitoes with honeybee DNA could tame malaria
23579R. Blakely, The Times, 2022-09-22 13:53:23.
A new form of genetically engineered mosquito could reduce the spread of malaria in Africa, a study suggests. The addition of DNA from a honeybee and genetic material from the African clawed frog prompt the new mosquitoes to produce compounds to stunt the growth of the parasite that causes malaria. This means that the parasite, and therefore the disease, is less likely to be passed on to human victims via mosquito bite. To be useful in the real world this would have to be coupled with an existing technology known as a gene drive, a controversial genetic tool that would force the new characteristic through populations of mosquitoes as they reproduce. For malaria to spread, a female mosquito must bite someone infected with the malaria
Genetically Engineered Mosquitoes Prevented the Growth of Malaria-causing Parasites in Their Gut
23576P. Mozter, Nature World News 2022, 2022-09-22 13:45:51.
Abstract: Scientists have created mosquitoes that inhibit the development of malaria-causing parasites in their stomachs, therefore decreasing disease transmission to people. The genetic change allows mosquitoes to create substances in their intestines that inhibit parasite development, making parasites less likely to reach the mosquitoes' salivary glands and be transmitted in a bite before the insects die, as per ScienceDaily. The Transmission: Zero team at Imperial College London developed the breakthrough so that it may be used with current "gene drive" technologies to distribute the alteration and substantially reduce malaria transmission. The team is planning field experiments, but first, they will rigorously verify the new modification's safety before merging it with a gene drive for real-world testing.
Fitness effects of CRISPR endonucleases in Drosophila melanogaster populations
23673A. M. Langmüller, J. Champer, S. Lapinska, L. Xie, M. Metzloff, S. E. Champer, J. Liu, Y. Xu, J. Du, A. G. Clark and P. W. Messer, eLife, 11:e71809. 2022-09-22 08:22:04.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 provides a highly efficient and flexible genome editing technology with numerous potential applications ranging from gene therapy to population control. Some proposed applications involve the integration of CRISPR/Cas9 endonucleases into an organism’s genome, which raises questions about potentially harmful effects to the transgenic individuals. One example for which this is particularly relevant are CRISPR-based gene drives conceived for the genetic alteration of entire populations. The performance of such drives can strongly depend on fitness costs experienced by drive carriers, yet relatively little is known about the magnitude and causes of these costs. Here, we assess the fitness effects of genomic CRISPR/Cas9 expression in Drosophila melanogaster cage populations by tracking allele frequencies of four different transgenic constructs that allow us to disentangle ‘direct’ fitness costs due to the integration, expression, and target-site activity of Cas9, from fitness costs due to potential off-target cleavage. Using a maximum likelihood framework, we find that a model with no direct fitness costs but moderate costs due to off-target effects fits our cage data best. Consistent with this, we do not observe fitness costs for a construct with Cas9HF1, a high-fidelity version of Cas9. We further demonstrate that using Cas9HF1 instead of standard Cas9 in a homing drive achieves similar drive conversion efficiency. These results suggest that gene drives should be designed with high-fidelity endonucleases and may have implications for other applications that involve genomic integration of CRISPR endonucleases.
Mosquitoes are being genetically modified so they can’t spread malaria
23596M. Le Page, New Scientist, 2022-09-21 14:17:06.
Gene editing mosquitoes so they die before malaria parasites can develop inside them could stop the spread of the deadly parasite entirely,
Scientists engineer mosquitoes that can’t spread malaria
23572Imperial College London, Phys Org, 2022-09-21 13:32:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria. The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing "gene drive" technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Extreme GM “extinction technology” of gene drives presented as “natural”
23625GM Watch, GM Watch, 2022-09-19 14:45:48.
Now similar Orwellian moves are happening in the area of gene drives. A gene drive is a genetic engineering technology that forces a particular genetic modification through a population by changing the natural rules of inheritance, usually to ensure that it is increasingly – or always – inherited. Gene drive organisms are built to intentionally spread their engineered traits through an entire population, turning on its head the usual imperative to try to contain and prevent engineered genes from contaminating and disrupting ecosystems. They can be designed to re-model or delete entire species. Gene drive technology is deeply unpopular and rightly feared by the public and regulators. It is against this background that in recent years, some researchers have begun to describe so-called "selfish genetic elements" found in nature* as "natural gene drives" and to present gene drive as a "ubiquitous natural phenomenon".
Daisy-chain gene drives: The role of low cut-rate, resistance mutations, and maternal deposition
23623S. A. N. Verkuijl, M. A. E. Anderson, L. Alphey and M. B. Bonsall, PLOS Genetics, 18:e1010370. 2022-09-19 14:37:34.
Author summary Reducing the harm of pest species by the introgression of traits into a wild population is often limited by the difficulties of mass rearing and release of modified individuals. Gene drives present an opportunity to substantially reduce the release frequencies required to spread a particular modification. However, uniform modification of a target species is, with a few specific exceptions, not necessary or desirable. Self-limiting gene drives, such as daisy-chain gene drives, have been widely discussed as a potential solution, allowing the invasiveness of a drive release to be tuned to the target population. Here, we investigate through computational modelling how daisy-chain gene drives perform when subjected to commonly observed inefficiencies associated with CRISPR-Cas9-based inheritance biasing. Compared to a self-perpetuating drive, daisy-chain gene drives are sensitive to factors that cause their separate elements to segregate prematurely. In particular, a reduction in the DNA cut-rate and an increase in the formation of resistance alleles. We find that the effect of inefficiencies in the drive mechanism is generally more pronounced when the drive is at low frequencies. With low rates of migration, this substantially reduces daisy-chain gene drives spread into a neighbouring non-target population.
Humans Have a Long History of Making ‘Very Bad Decisions’ to Save Animals
23627T. McDonnell, The New York Times, 2022-09-17 07:17:21.
Environmental reporter Tim McDonnell on the potential negative consequences of animal conservation efforts. McDonnell highlights Target Malaria’s research on gene drive to “eliminate malaria-carrying mosquitos” and quotes New Zealand researcher Philipp Messer saying that the world is “ill-prepared” for a "real-life gene drive.” The article also quotes MIT biologist Kevin Esvelt saying that misuse of the technology would cause the public and policymakers to halt gene drive research and would set the field back by a decade. The article notes that there is no international regulation to “prevent the premature deployment of gene drive in the wild” and states that “individual governments, powerful funding organizations like the Bill and Melinda Gates Foundation, and scientists themselves” are responsible for balancing the prevention of risky interventions with the need to support basic research. Esvlet is also quoted saying that the WHO needs to “establish a registry for all gene drive experiments that requires scientists to detail safeguards and find a local community who agrees to guide the research before experiments begin.”
A detailed landscape of CRISPR-Cas-mediated plant disease and pest management
23532S. Karmakar, P. Das, D. Panda, K. Xie, M. J. Baig and K. A. Molla, Plant Science, 323:111376. 2022-09-09 05:44:18.
Genome editing technology has rapidly evolved to knock-out genes, create targeted genetic variation, install precise insertion/deletion and single nucleotide changes, and perform large-scale alteration. The flexible and multipurpose editing technologies have started playing a substantial role in the field of plant disease management. CRISPR-Cas has reduced many limitations of earlier technologies and emerged as a versatile toolbox for genome manipulation. This review summarizes the phenomenal progress of the use of the CRISPR toolkit in the field of plant pathology. CRISPR-Cas toolbox aids in the basic studies on host-pathogen interaction, in identifying virulence genes in pathogens, deciphering resistance and susceptibility factors in host plants, and engineering host genome for developing resistance. We extensively reviewed the successful genome editing applications for host plant resistance against a wide range of biotic factors, including viruses, fungi, oomycetes, bacteria, nematodes, insect pests, and parasitic plants. Recent use of CRISPR-Cas gene drive to suppress the population of pathogens and pests has also been discussed. Furthermore, we highlight exciting new uses of the CRISPR-Cas system as diagnostic tools, which rapidly detect pathogenic microorganism. This comprehensive yet concise review discusses innumerable strategies to reduce the burden of crop protection.
Applications of gene drive systems for population suppression of insect pests
23503M. Asad, D. Liu, J. Chen and G. Yang, Bulletin of Entomological Research, 2022-08-31 19:19:28.
Population suppression is an effective way for controlling insect pests and disease vectors, which cause significant damage to crop and spread contagious diseases to plants, animals and humans. Gene drive systems provide innovative opportunities for the insect pests population suppression by driving genes that impart fitness costs on populations of pests or disease vectors. Different gene-drive systems have been developed in insects and applied for their population suppression. Here, different categories of gene drives such as meiotic drive (MD), under-dominance (UD), homing endonuclease-based gene drive (HEGD) and especially the CRISPR/Cas9-based gene drive (CCGD) were reviewed, including the history, types, process and mechanisms. Furthermore, the advantages and limitations of applying different gene-drive systems to suppress the insect population were also summarized. This review provides a foundation for developing a specific gene-drive system for insect population suppression.
ISAAA Policy Brief: Risk Assessment for Gene Drive Organisms
23562Anonymous, ISAAA, 2022-08-31 14:52:33.
Gene drive is a genetic phenomenon that occurs in nature and causes a selected trait to spread rapidly through a species via sexual reproduction over generations, potentially becoming increasingly common within a specific species. Gene drive systems are being developed in the laboratory to replicate this natural phenomenon in order to help tackle major challenges such as malaria. In this way, a desired change is passed on to up to 100% of offspring, rather than at the more usual rate of 50%. This technology is currently under research, and the risks and benefits of each potential application are being thoroughly investigated.
A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae
23500A. L. Smidler, J. J. Pai, R. A. Apte, H. M. Sánchez C, R. M. Corder, E. J. Gutiérrez, N. Thakre, I. Antoshechkin, J. M. Marshall and O. S. Akbari, bioRxiv, 2022.08.30.505861. 2022-08-30 19:10:47.
Malaria is among the world’s deadliest diseases, predominantly affecting sub-Saharan Africa, and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here we develop an innovative genetic population suppression system termed Ifegenia (Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we show that Ifegenia males remain reproductively viable, and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of non-biting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.
Genetic Tools for Integrated Management of Pests on Honeybees in the Tropics
25464M. Pattabhiramaiah, S. Mallikarjunaiah and D. Brueckner, Genetic Methods and Tools for Managing Crop Pests, 2022-08-22 09:48:31.
The Asian honeybee is endemic to Asia where it has been used for honey production and pollination services from time immemorial. They are integral to modern agricultural productivity and to survival and vitality of natural ecosystems. However, recent declines in populations and species diversity threaten both food security and natural habitats. Honeybee colonies are assaulted by numerous pests and pathogens including mites and beetles. Novel, cost-effective pest management practices are desperately needed to preserve colony health. Increased pest pressure levels justify the need for additional control methods. Beekeepers should follow the guidelines of integrated pest management (IPM) as an effective control option that will have a minimum impact on honeybee health. The use of genomic tools and engineering technologies has a great potential for enhancement and sustenance of the health of honeybees. This review focusses on the application of innovative advanced genetic tools such as SIT (sterile insect technique), genome editing, gene drive, RNAi, CRISPR/Cas9-mediated gene editing, and gene pyramiding in honeybee pest management.
Environmentally appropriate vector control is facilitated by standard metrics for simulation-based evaluation
23443V. N. Vásquez, M. R. Reddy and J. M. Marshall, Frontiers in Tropical Diseases, 3. 2022-08-17 08:44:11.
As anthropogenic factors contribute to the introduction and expansion of new and established vector species, the geographic incidence of mosquito-borne disease is shifting. Computer simulations, informed by field data where possible, facilitate the cost-effective evaluation of available public health interventions and are a powerful tool for informing appropriate policy action. However, a variety of measurements are used in such assessments; this can complicate direct comparisons across both vector control technologies and the models used to simulate them. The expansion of biocontrol to include genetically engineered organisms is now prompting additional metrics with no analogy to traditional measurement approaches. We propose Standard Entomological Metrics (SEMs) to facilitate the model-based appraisal of both existing and novel intervention tools and define two examples: Suppression Efficacy Score and Time to Reduction Target. We formulate twelve synthetic case studies featuring two vector control technologies over three years of observed daily temperature in Cairns, Australia. After calculating Suppression Efficacy Score and Time to Reduction Target results, we apply these example outcomes to a discussion of health policy decision-making using SEMs. We submit that SEMs such as Suppression Efficacy Score and Time to Reduction Target facilitate the wholistic and environmentally appropriate simulation-based evaluation of intervention programs and invite the community to further discussion on this topic.
A multiplexed, confinable CRISPR/Cas9 gene drive propagates in caged Aedes aegypti populations
23429M. A. E. Anderson, E. Gonzalez, M. P. Edgington, J. X. D. Ang, D.-K. Purusothaman, L. Shackleford, K. Nevard, S. A. N. Verkuijl, T. Harvey-Samuel, P. T. Leftwich, K. Esvelt and L. Alphey, bioRxiv, 2022.08.12.503466. 2022-08-12 07:19:58.
Here, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 in the germline to find an expression timing more conducive to homing. We also created a separate multiplexing (targeting multiple different sites within the target gene) sgRNA-expressing homing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene to limit the consequences of resistance alleles. This creates a ‘split’ gene drive such that one part does not drive, allowing control over geographic spread and temporal persistence. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element was driven through a cage trial population such that carrier frequency of the element increased from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.Significance statement Mosquito-borne diseases affect millions of people worldwide, with the yellow fever mosquito (Aedes aegypti) being the principal vector of many viral diseases. Effective measures for controlling this mosquito are sorely needed. Gene drive systems have arisen as a potential tool for mosquito control due to their ability of biasing inheritance of a trait into a target population. Here, we assess a split gene drive, based on CRISPR/Cas9 endonuclease technology driving a target element into the mosquito population. Evaluated over successive generations in a replicated cage trial, the drive successfully biased its inheritance, increasing in frequency from 50% to up to 89%. Our results are encouraging for the potential use of this type of contained gene drive system for mosquito control in endemic areas.Competing Interest StatementThe authors have declared no competing interest.
Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: a modeling study
23424J. Li and J. Champer, bioRxiv, 2022.08.09.503337. 2022-08-11 07:25:47.
By using both mathematical and simulation models, we found that a drive containing CifA and CifB together create a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence.
Reflection on the Challenges, Accomplishments, and New Frontiers of Gene Drives
23416M. Melesse Vergara, J. Labbé and J. Tannous, BioDesign Research, 2022:9853416. 2022-08-09 07:29:59.
Ongoing pest and disease outbreaks pose a serious threat to human, crop, and animal lives, emphasizing the need for constantgenetic discoveries that could serve as mitigation strategies. Gene drives are genetic engineering approaches discovered decadesago that may allow quick, super-Mendelian dissemination of genetic modifications in wild populations, offering hopes formedicine, agriculture, and ecology in combating diseases. Following itsfirst discovery, several naturally occurring selfishgenetic elements were identified and several gene drive mechanisms that could attain relatively high threshold populationreplacement have been proposed. This review provides a comprehensive overview of the recent advances in gene drive researchwith a particular emphasis on CRISPR-Cas gene drives, the technology that has revolutionized the process of genomeengineering. Herein, we discuss the benefits and caveats of this technology and place it within the context of natural genedrives discovered to date and various synthetic drives engineered. Later, we elaborate on the strategies for designing syntheticdrive systems to address resistance issues and prevent them from altering the entire wild populations. Lastly, we highlight themajor applications of synthetic CRISPR-based gene drives in different living organisms, including plants, animals, andmicroorganisms.
A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variation
23362B. S. Khatri and A. Burt, Proceedings of the National Academy of Sciences, 119:e2200567119. 2022-08-01 07:26:58.
CRISPR-based gene drives have the potential for controlling natural populations of disease vectors, such as malaria-carrying mosquitoes in sub-Saharan Africa. If successful, they hold promise of significantly reducing the burden of disease and death from malaria and many other vector-borne diseases. A significant challenge to success is the evolution of resistance. Here, we develop a theory of resistance for multiplexed drive, which shows the importance of weakly deleterious naturally occurring genetic variation, whose effect is significantly amplified compared to de novo mutation. These results provide a fundamental basis to estimate how many guide RNAs are required to prevent resistance in the face of natural genetic variation. Evolution of resistance is a major barrier to successful deployment of gene-drive systems to suppress natural populations, which could greatly reduce the burden of many vector-borne diseases. Multiplexed guide RNAs (gRNAs) that require resistance mutations in all target cut sites are a promising antiresistance strategy since, in principle, resistance would only arise in unrealistically large populations. Using stochastic simulations that accurately model evolution at very large population sizes, we explore the probability of resistance due to three important mechanisms: 1) nonhomologous end-joining mutations, 2) single-nucleotide mutants arising de novo, or 3) single-nucleotide polymorphisms preexisting as standing variation. Our results explore the relative importance of these mechanisms and highlight a complexity of the mutation?selection?drift balance between haplotypes with complete resistance and those with an incomplete number of resistant alleles. We find that this leads to a phenomenon where weakly deleterious naturally occurring variants greatly amplify the probability of multisite resistance compared to de novo mutation. This key result provides design criterion for antiresistance multiplexed systems, which, in general, will need a larger number of gRNAs compared to de novo expectations. This theory may have wider application to the evolution of resistance or evolutionary rescue when multiple changes are required before selection can act.
What do we mean by “Target Organism” in Target Malaria’s gene drive research?
23336J. B. Connolly, Target Malaria, 2022-07-27 08:46:32.
In the wild and in laboratory settings, sibling mosquito species can successfully mate to produce viable offspring, regardless of whether they are vectors or not. Importantly, females, but not males, of these offspring can be fertile. Nonetheless, the likelihood of finding such hybrid mosquitoes in field samples varies greatly between different combinations of species. According to some field studies, typically, only about 0.1% of mosquito collected in the wild could be An. gambiae s.s./An. coluzzii hybrids. In addition, some species that do not overlap geographically, and therefore would not come into direct contact, cannot produce hybrids in the field. This includes An. melas, which is found along the coast of West Africa, and An. bwambae, which is restricted to hot springs in the Toro District of Uganda. This means that the gene drive could eventually transfer to all sibling species of the complex, both by direct hybridisation between geographically-overlapping species and, indirectly, by transferring from one species to another overlapping ones like stepping-stones until the gene drive was transferred to all species of the complex, including to the likes of An. melas and An. bwambae
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study
23307S. Leung, N. Windbichler, E. A. Wenger, C. A. Bever and P. Selvaraj, Malaria Journal, 21:226. 2022-07-26 07:49:07.
BACKGROUND: Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa. METHODS: Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems-"classic" and "integral"-are evaluated. Various transmission regimes (low, moderate, and high-corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated. RESULTS: Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80-90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80-90%. CONCLUSION: A single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.
Operationalizing stakeholder engagement for gene drive research in malaria elimination in Africa-translating guidance into practice
23281L. Pare Toe, B. Dicko, R. Linga, N. Barry, M. Drabo, N. Sykes and D. Thizy, Malaria Journal, 21:225. 2022-07-23 10:16:04.
Gene drive mosquitoes are increasingly considered a potential transformational tool for vector control of malaria mosquitoes. As part of efforts to promote responsible research in this field, a number of guidance documents have been published by the World Health Organization, National Academies and expert groups. While virtually all recent guidance documents on gene drive research stress the importance of stakeholder engagement activities, no specific guidelines on implementing them have been established. Target Malaria, a not-for-profit research consortium developing a vector-control gene drive approach to eliminate malaria, has reflected on how its stakeholder engagement strategy translates engagement guidance documents into practice. The project analysed and addressed the tension between the context specificities and the international recommendations. The engagement strategy combines published recommendations for responsible gene drive research, information collected from the local context where the project operates and a set of principles guiding the choices made. This strategy was first developed during the early phases of the project's research, years ahead of any activities with gene drive mosquitoes in those countries of operations. These earlier activities, and their related engagement, allow the project to develop and adapt an engagement strategy appropriate for potential gene drive research in its field site countries. This paper offers a description of a stakeholder engagement strategy operationalization based on (1) adaptation to stakeholder preferences, (2) inclusiveness and (3) empowerment and accountability. The authors hope to offer concrete examples to support other projects with the development and implementation of their engagement strategies with particular attention to the co-development principle.
Comprehensive characterization of a transgene insertion in a highly repetitive, centromeric region of Anopheles mosquitoes
23273M. Vitale, C. Leo, T. Courty, N. Kranjc, J. B. Connolly, G. Morselli, C. Bamikole, R. E. Haghighat-Khah, F. Bernardini and S. Fuchs, Pathogens and Global Health, 2022-07-21 07:55:48.
The availability of the genomic sequence of the malaria mosquito Anopheles gambiae has in recent years sparked the development of transgenic technologies with the potential to be used as novel vector control tools. These technologies rely on genome editing that confer traits able to affect vectorial capacity. This can be achieved by either reducing the mosquito population or by making mosquitoes refractory to the parasite infection. For any genetically modified organism that is regarded for release, molecular characterization of the transgene and flanking sites are essential for their safety assessment and post-release monitoring. Despite great advancements, Whole-Genome Sequencing data are still subject to limitations due to the presence of repetitive and unannotated DNA sequences. Faced with this challenge, we describe a number of techniques that were used to identify the genomic location of a transgene in the male bias mosquito strain Ag(PMB)1 considered for potential field application. While the initial inverse PCR identified the most likely insertion site on Chromosome 3 R 36D, reassessment of the data showed a high repetitiveness in those sequences and multiple genomic locations as potential insertion sites of the transgene. Here we used a combination of DNA sequencing analysis and in-situ hybridization to clearly identify the integration of the transgene in a poorly annotated centromeric region of Chromosome 2 R 19D. This study emphasizes the need for accuracy in sequencing data for the genome of organisms of medical importance such as Anopheles mosquitoes and other tools available that can support genomic locations of transgenes.
Development of CRISPR/Cas9-Mediated Gene-Drive Construct Targeting the Phenotypic Gene in Plutella xylostella
23265M. Asad, D. Liu, J. Li, J. Chen and G. Yang, Frontiers in Physiology, 13:938621. 2022-07-20 13:03:05.
The gene-drive system can ensure that desirable traits are transmitted to the progeny more than the normal Mendelian segregation. The clustered regularly interspersed palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mediated gene-drive system has been demonstrated in dipteran insect species, including Drosophila and Anopheles, not yet in other insect species. Here, we have developed a single CRISPR/Cas9-mediated gene-drive construct for Plutella xylostella, a highly-destructive lepidopteran pest of cruciferous crops. The gene-drive construct was developed containing a Cas9 gene, a marker gene (EGFP) and a gRNA sequence targeting the phenotypic marker gene (Pxyellow) and site-specifically inserted into the P. xylostella genome. This homing-based gene-drive copied ∼12 kb of a fragment containing Cas9 gene, gRNA, and EGFP gene along with their promoters to the target site. Overall, 6.67%-12.59% gene-drive efficiency due to homology-directed repair (HDR), and 80.93%-86.77% resistant-allele formation due to non-homologous-end joining (NHEJ) were observed. Furthermore, the transgenic progeny derived from male parents showed a higher gene-drive efficiency compared with transgenic progeny derived from female parents. This study demonstrates the feasibility of the CRISPR/Cas9-mediated gene-drive construct in P. xylostella that inherits the desired traits to the progeny. The finding of this study provides a foundation to develop an effective CRISPR/Cas9-mediated gene-drive system for pest control.
Novel gene drive based on eliciting piRNA biogenesis in insect pests
23235C. Henderson and B. Christina, Rutgers Research, 2022-07-14 06:56:49.
Rutgers researchers have developed a potential permanent solution to persistent pest control issues by developing a system for genetic modification which could reduce the transmission of vector borne diseases (like malaria) from their insect vectors, or to establish expression of a desirable trait such as Bacillus thuringiensis susceptibility in crop pests. The inventors have demonstrated their solution through a transgenic construct that expresses an anti-malaria peptide in Anopheles gambiae alongside piRNAs which are designed to direct silencing towards a host gene required for reproduction. If the host silences the genetic construct, this silencing will be directed towards the host gene resulting in infertility. This platform can be used to create a gene drive that can prevent resistance formation and allow for rapid spread of a trait within a population
Gene Drive in Species Complexes: Defining Target Organisms
23207J. B. Connolly, J. Romeis, Y. Devos, D. C. M. Glandorf, G. Turner and M. B. Coulibaly, Trends in Biotechnology, 2022-07-12 06:21:17.
Engineered gene drives, which bias their own inheritance to increase in frequency in target populations, are being developed to control mosquito malaria vectors. Such mosquitoes can belong to complexes of both vector and non-vector species that can produce fertile interspecific hybrids, making vertical gene drive transfer (VGDT) to sibling species biologically plausible. While VGDT to other vectors could positively impact human health protection goals, VGDT to non-vectors might challenge biodiversity ones. Therefore, environmental risk assessment of gene drive use in species complexes invites more nuanced considerations of 'Target Organisms' and ‘Non-Target Organisms' than for transgenes not intended to increase in frequency in target populations. Incorporating the concept of ‘Target Species Complexes’ offers more flexibility when assessing potential impacts from VGDT.
Genetically-enhanced biocontrols can help fight large invasive mammals
23157Pensoft Publishers, Science Daily, 2022-07-08 09:49:27.
A team of researchers from the University of Adelaide developed a mathematical model able to simulate the impact of gene drives on mammal populations at a landscape scale. Published in the open-access NeoBiotajournal, their study is the first to estimate the time it would take to eradicate long-lived alien mammals. Using CRISPR-Cas9 technology, the simulated gene drive relies on "molecular scissors" inserted into the Y-chromosome that target and slice up the X-chromosome at the right time during meiosis, so that only Y-chromosome carrying sperms are functional and can successfully fertilize the egg. In this way, the drive carrying males should only produce sons that also carry the molecular scissors on their Y-chromosome. Over multiple generations, females will become rarer and produce fewer offspring; as a result, the population size will fall.
Gene drives and Africa’s battle against malaria
23154Annonymous, Africa Verified, 2022-07-08 09:43:10.
As malaria cases rise, and the effectiveness of current methods begins to fall, the WHO’s target of reducing the global malaria burden by 90% by 2030 will not be met. It is critical for new and resilient treatment, prevention, and control methods to be developed and integrated into current strategies. Target Malaria is a not-for-profit research consortium aiming to develop ‘cost-effective and sustainable genetic technologies to modify mosquitoes and reduce malaria transmission’ that would work alongside current anti-malaria efforts. They are pioneering research into genetically programmed mosquitoes, which when released into the wild to mate, reproduce offspring that either produce fewer female mosquitoes or are unable to transmit malaria parasites.
A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes
23150E. I. Green, E. Jaouen, D. Klug, R. P. Olmo, A. Gautier, S. A. Blandin and E. Marois, bioRxiv, 2022.07.08.499187. 2022-07-08 09:32:53.
Lipophorin is an essential, highly expressed lipid transporter protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles gambiae Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild type Lipophorin, causing the anti-malarial modified Lipophorin version to hitch-hike together with the Saglin drive. Although producing drive-resistant alleles, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to affect parasite transmission by two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.Competing Interest StatementThe authors have declared no competing interest.
Scalability of genetic biocontrols for eradicating invasive alien mammals
23159A. Birand, P. Cassey, J. V. Ross, P. Q. Thomas and T. A. A. Prowse, NeoBiota, 74:93-103. 2022-07-07 09:59:20.
CRISPR-based gene drives offer novel solutions for controlling invasive alien species, which could ultimately extend eradication efforts to continental scales. Gene drives for suppressing invasive alien vertebrates are now under development. Using a landscape-scale individual-based model, we present the first estimates of times to eradication for long-lived alien mammals. We show that demography and life-history traits interact to determine the scalability of gene drives for vertebrate pest eradication. Notably, optimism around eradicating smaller-bodied pests (rodents and rabbits) with gene-drive technologies does not easily translate into eradication of larger-bodied alien species (cats and foxes).
Larval mosquito management and risk to aquatic ecosystems: A comparative approach including current tactics and gene-drive Anopheles techniques
23152R. K. D. Peterson and M. G. Rolston, Transgenic Research, 2022-07-07 09:39:09.
Genetic engineering of mosquitoes represents a promising tactic for reducing human suffering from malaria. Gene-drive techniques being developed that suppress or modify populations of Anopheles gambiae have the potential to be used with, or even possibly obviate, microbial and synthetic insecticides. However, these techniques are new and therefore there is attendant concern and uncertainty from regulators, policymakers, and the public about their environmental risks. Therefore, there is a need to assist decision-makers and public health stewards by assessing the risks associated with these newer mosquito management tactics so the risks can be compared as a basis for informed decision making. Previously, the effect of gene-drive mosquitoes on water quality in Africa was identified as a concern by stakeholders. Here, we use a comparative risk assessment approach for the effect of gene-drive mosquitoes on water quality in Africa. We compare the use of existing larvicides and the proposed genetic techniques in aquatic environments. Based on our analysis, we conclude that the tactic of gene-drive Anopheles for malaria management is unlikely to result in risks to aquatic environments that exceed current tactics for larval mosquitoes. As such, these new techniques would likely comply with currently recommended safety standards.
Do Australians support genetic technology to control feral animals?
23095E. Phiddian, COSMOS, 2022-07-02 07:43:33.
Synthetic biology and genetic technology could be a safer, more humane way of curbing invasive species. Feral cat populations, for instance, could be controlled by preventing them from breeding. But there’s no point trying a new technology it if it doesn’t have public support – so does synthetic biology pass the pub test? According to a report from the CSIRO, it just might. Their survey of nearly 4,000 Australians finds that most support the idea of using gene drives on feral cats.“This particular study builds on our public acceptability work over the last three to four years on synthetic biology solutions to significant national challenges,” says Dr Aditi Mankad, co-author of the report and a researcher at CSIRO Land & Water’s Sustainability Pathways Program.
Public perspectives towards using gene drive for invasive species management in Australia
23100A. Mankad, E. V. Hobman and L. Carter, CSIRO, 2022-06-30 07:55:31.
Many pest animal species live and reproduce in high numbers across Australia. This includes animal species, such as cane toads, feral cats, foxes, rodents, wild pigs, wild rabbits. These species significantly damage Australia’s agricultural industries, natural landscapes, and biodiversity. For example, feral cats kill an estimated 1.8 billion Australian animals every year. Feral animals can also carry livestock diseases and cause significant damage to land and native vegetation. This results in agricultural production losses of more than $800 million per year. Sites of cultural significance to Indigenous peoples are also at risk to pest incursions. Adding further complexity, current methods of pest control being used to manage local landscape, such as baiting, trapping and shooting, are labour-intensive and expensive. They also have animal welfare implications and are considered ineffective at scale. Genetic technologies that are developed using synthetic biology have the potential to reduce or in some cases eliminate populations of invasive pests in parts of Australia. But there are multiple social, cultural and institutional considerations to understand before genetic technologies could feasibly be integrated with current pest management practices.
Breeding out the feral cat problem
23097S. Schmidt, ECOS, 2022-06-30 07:48:16.
While feral cats have only existed as part of Australia’s ecosystem for the last 200 or so years, they’ve left a destructive mark on our landscape. They’ve contributed to a growing list of Australian native animals that have become threatened or extinct in that time. Today, feral cats (Felis catus) are rampant in all parts of Australia, covering 99% of Australia’s total land area. That includes ecosystems from deserts to forests and grasslands, and even many of our offshore islands. Though they might share their species name and genome with their domestic counterparts, that’s where their similarity ends, explains Biosecurity Research Director at CSIRO, Dr Raghu Sathyamurthy. “Feral cats are opportunistic predators. They’re one of the most significant threats to our native species including small mammals, birds and reptiles,” says Dr Sathyamurthy.
The suppressive potential of a gene drive in populations of invasive social wasps is currently limited
23091A. B. Meiborg, N. R. Faber, B. A. Taylor, B. A. Harpur and G. Gorjanc, bioRxiv, 2022.06.27.497711. 2022-06-30 07:33:43.
Social insects are very successful invasive species, and the continued increase of global trade and transportation has exacerbated this problem. The yellow-legged hornet, Vespa velutina nigrithorax (henceforth Asian hornet), is drastically expanding its range in Western Europe. As an apex insect predator, this hornet poses a serious threat to the honey bee industry and endemic pollinators. Current suppression methods have proven too inefficient and expensive to limit its spread. Gene drives might be an effective tool to control this species, but their use has not yet been thoroughly investigated in social insects. Here, we built a model that matches the hornet’s life history and modelled the effect of different gene drive scenarios on an established invasive population. To test the broader applicability and sensitivity of the model, we also incorporated the invasive European paper wasp Polistes dominula. We find that although a gene drive can spread through a social wasp population, it can only do so under stringent gene drive-specific conditions. The main issue is that the large number of offspring that social wasp colonies produce guarantees that, even with very limited formation of resistance alleles, such alleles will quickly spread and rescue the population. Furthermore, we find that only a gene drive targeting female fertility is promising for population control due to the haplodiploidy of social insects. Nevertheless, continued improvements in gene drive technology may make it a promising method for the control of invasive social insects.Competing Interest StatementThe authors have declared no competing interest.
Australians open to using genetic technology to manage feral cats
23086CSIRO, MIRAGE, 2022-06-30 07:20:05.
New genetic technologies could help address the rise of invasives through a number of ways, one of which is called gene drive. Gene drive can determine the sex of offspring, reducing the number of animals able to reproduce, and therefore over time driving down populations. Researchers from CSIRO surveyed more than 3,800 people across Australia to understand public perceptions of using gene drive on feral cats. The research found 86 per cent of people were at least moderately supportive for the local implementation of gene drive technology to manage invasive feral cat species in their local area.
Public deliberation and the regulation of gene drive in the USA
23131W. F. West, L. W. Buchman and R. F. Medina, Science and Public Policy, scac032. 2022-06-27 10:41:33.
Gene drive is a new form of biotechnology designed to bias the inheritance of selected traits in animal or plant species that reproduce sexually and have relatively short reproductive cycles. Unlike traditional breeding techniques and other forms of biotechnology, gene drive is designed to spread in wild populations. As such, the prospect of its application raises ecological and socioeconomic concerns that the current system of biotechnology regulation in the USA is ill-equipped to address. Foremost among the proposals for reform is the need for deliberative participation in decision-making by stakeholders representing a broader range of interests and analytical perspectives. As appealing as they are in the abstract, these recommendations overlook both practical and political challenges to democratic governance in administration that have received little attention.
DriverSEAT: A spatially-explicit stochastic modelling framework for the evaluation of gene drives in novel target species
23008M. Legros and L. G. Barrett, bioRxiv, 2022.06.13.496025. 2022-06-16 08:19:49.
Gene drives represent a potentially ground breaking technology for the control of undesirable species or the introduction of desirable traits in wild population, and there is strong interest in applying these technologies to a wide range of species across many domains including agriculture, health, conservation and biosecurity. There remains however considerable uncertainty regarding the feasibility and efficacy of gene drives in various species, based in particular on biological and ecological specificities of each target. In this paper we introduce DriverSEAT, a new spatial, modular modelling framework designed to assess the outcome of gene drives in a range of target species based on their specific ecological dynamics and genetics. In addition to the main structure and characteristics of the model, we present an example of its application on scenarios of genetic control of weeds, a potential candidate for gene drive control that presents significant challenges associated with plant population dynamics. We illustrate here how the results from DriverSEAT can inform on the potential value of gene drives in this specific context, and generally provide ecologically informed guidance for the development and feasibility of gene drives as a control method in new target species.Competing Interest StatementThe authors have declared no competing interest.
Natural and Engineered Sex Ratio Distortion in Insects
23010A. Compton and Z. Tu, Frontiers in Ecology and Evolution, 10. 2022-06-15 08:25:52.
Insects have evolved highly diverse genetic sex-determination mechanisms and a relatively balanced male to female sex ratio is generally expected. However, selection may shift the optimal sex ratio while meiotic drive and endosymbiont manipulation can result in sex ratio distortion (SRD). Recent advances in sex chromosome genomics and CRISPR/Cas9-mediated genome editing brought significant insights into the molecular regulators of sex determination in an increasing number of insects and provided new ways to engineer SRD. We review these advances and discuss both naturally occurring and engineered SRD in the context of the Anthropocene. We emphasize SRD-mediated biological control of insects to help improve One Health, sustain agriculture, and conserve endangered species.
Generation of Gene Drive Mice for Invasive Pest Population Suppression
22890M. D. Bunting, C. Pfitzner, L. Gierus, M. White, S. Piltz and P. Q. Thomas, Applications of Genome Modulation and Editing, 2022-06-14 06:00:54.
Gene drives are genetic elements that are transmitted to greater than 50% of offspring and have potential for population modification or suppression. While gene drives are known to occur naturally, the recent emergence of CRISPR-Cas9 genome-editing technology has enabled generation of synthetic gene drives in a range of organisms including mosquitos, flies, and yeast. For example, studies in Anopheles mosquitos have demonstrated >95% transmission of CRISPR-engineered gene drive constructs, providing a possible strategy for malaria control. Recently published studies have also indicated that it may be possible to develop gene drive technology in invasive rodents such as mice. Here, we discuss the prospects for gene drive development in mice, including synthetic “homing drive” and X-shredder strategies as well as modifications of the naturally occurring t haplotype. We also provide detailed protocols for generation of gene drive mice through incorporation of plasmid-based transgenes in a targeted and non-targeted manner. Importantly, these protocols can be used for generating transgenic mice for any project that requires insertion of kilobase-scale transgenes such as knock-in of fluorescent reporters, gene swaps, overexpression/ectopic expression studies, and conditional “floxed” alleles.
Selective targeting of biting females to control mosquito-borne infectious diseases
22953B. B. Kojin, A. Compton, Z. N. Adelman and Z. Tu, Trends in Parasitology, 2022-06-13 06:48:00.
Mosquitoes are vectors for a number of infectious diseases. Only females feed on blood to provision for their embryos and, in doing so, transmit pathogens to the associated vertebrate hosts. Therefore, sex is an important phenotype in the context of genetic control programs, both for sex separation in the rearing facilities to avoid releasing biting females and for ways to distort the sex ratio towards nonbiting males. We review recent progress in the fundamental knowledge of sex determination and sex chromosomes in mosquitoes and discuss new methods to achieve sex separation and sex ratio distortion to help control mosquito-borne infectious diseases. We conclude by suggesting a few critical areas for future research.
Gene Drives: A Potentially New Weapon Against Mosquitoes
22905M. Sherman, Times Union Online, 2022-06-13 06:36:32.
Scientists have studied gene drives for more than 50 years, and to most of us this has been a well-kept secret. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussions of the potential applications and implications of gene drive technologies. Just prior to the beginning of this study and since the committee was first convened, scientists published four proofs of concept — one in yeast, one in fruit flies, and two in different species of mosquitoes — that demonstrate the successful development of gene drives in the laboratory, at least in these organisms.Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as gene editing tools become more refined. Gene-drive modified organisms are on the horizon. With mosquitoes, the gene drive interferes with the insect’s ability to reproduce. It wiped out captive populations in eight or 12 generations. The first experimental release could be rolled out in Burkina Faso, Mali, Ghana or Uganda.
Unbalanced selection: the challenge of maintaining a social polymorphism when a supergene is selfish
22895A. G. Tafreshi, S. P. Otto and M. Chapuisat, Philos Trans R Soc Lond B Biol Sci, 377:20210197. 2022-06-13 06:11:36.
Supergenes often have multiple phenotypic effects, including unexpected detrimental ones, because recombination suppression maintains associations among co-adapted alleles but also allows the accumulation of recessive deleterious mutations and selfish genetic elements. Yet, supergenes often persist over long evolutionary periods. How are such polymorphisms maintained in the face of selection, drive and drift? We present a population genetic model that investigates the conditions necessary for a stable polymorphic equilibrium when one of the supergene haplotypes is a selfish genetic element. The model fits the characteristics of the Alpine silver ant, Formica selysi, in which a large supergene underlies colony social organization, and one haplotype distorts Mendelian transmission by killing progeny that did not inherit it. The model shows that such maternal-effect killing strongly limits the maintenance of social polymorphism. Under random mating, transmission ratio distortion prevents rare single-queen colonies from invading populations of multiple-queen colonies, regardless of the fitness of each genotype. A stable polymorphic equilibrium can, however, be reached when high rates of assortative mating are combined with large fitness differences among supergene genotypes. The model reveals that the persistence of the social polymorphism is non-trivial and expected to occur only under restrictive conditions that deserve further empirical investigation. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Active genetics comes alive
22888V. M. Gantz and E. Bier, BioEssays, 2022-06-09 09:28:52.
Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based ?active genetic? elements developed in 2015 bypassed the fundamental rules of traditional genetics. Inherited in a super-Mendelian fashion, such selfish genetic entities offered a variety of potential applications including: gene-drives to disseminate gene cassettes carrying desired traits throughout insect populations to control disease vectors or pest species, allelic drives biasing inheritance of preferred allelic variants, neutralizing genetic elements to delete and replace or to halt the spread of gene-drives, split-drives with the core constituent Cas9 endonuclease and guide RNA (gRNA) components inserted at separate genomic locations to accelerate assembly of complex arrays of genetic traits or to gain genetic entry into novel organisms (vertebrates, plants, bacteria), and interhomolog based copying systems in somatic cells to develop tools for treating inherited or infectious diseases. Here, we summarize the substantial advances that have been made on all of these fronts and look forward to the next phase of this rapidly expanding and impactful field.
Genetically Modified Mosquitoes to Fight Malaria in Nigeria, Burkina Faso, Mali and Uganda: What Legal Response?
23275O. J. L. Tung, Potchefstroom Electronic Law Journal, 25:1-42. 2022-06-07 10:05:47.
Advanced applied research on genetically modified (hereafter GM) insects is being undertaken to control insect vectors of human diseases such as mosquitoes. GM insect technologies are being developed in countries where there is a legal framework for genetically modified mosquitoes (hereafter GMM), but the beneficiaries of such insect technologies to control insect-borne diseases are most likely to be in malaria-endemic countries where the regulation of GM insect technologies is inadequate. Although no commercial release of GMM has been conducted in Africa yet, there may be prospects for the use of GMM to control malaria in malaria-endemic countries such as Nigeria, Burkina Faso, Mali and Uganda. Nigeria has the highest rate of deaths related to malaria in Africa and will potentially be targeted by companies seeking to introduce GMM as a public health tool in African countries. Research is being carried out on GMM in Burkina Faso, Mali and Uganda in collaboration with foreign companies. Whereas the control of diseases is certainly needed and there are potential public health benefits for GM insect technologies to address mosquito control, there are environmental and health concerns, and there is also the potential of the misuse of such technologies. Consequently, the use of GMM requires prior robust domestic, regional and international regulation. While the Cartagena Protocol on Transboundary Movements of Living Modified Organisms (LMOs) to the Convention on Biological Diversity (hereafter the Cartagena Protocol)and voluntary guidelines on the testing of GM mosquitoes are applicable with respect to GM insect technologies, there is a lack of international and regional guidance on the regulation of such technologies. Domestic legislation tends to focus on GM crops and is inadequate for regulating GMM. This paper discusses the legal response for the above Africancountries which may perhaps use GMM as a public health tool and makes recommendations for the necessary regulatory response
Investigating CRISPR/Cas9 gene drive for production of disease-preventing prion gene alleles
22796A. R. Castle, S. Wohlgemuth, L. Arce and D. Westaway, PLoS One, 17:e0269342. 2022-06-07 09:14:53.
Prion diseases are a group of fatal neurodegenerative disorders that includes chronic wasting disease, which affects cervids and is highly transmissible. Given that chronic wasting disease prevalence exceeds 30% in some endemic areas of North America, and that eventual transmission to other mammalian species, potentially including humans, cannot be ruled out, novel control strategies beyond population management via hunting and/or culling must be investigated. Prion diseases depend upon post-translational conversion of the cellular prion protein, encoded by the Prnp gene, into a disease-associated conformation; ablation of cellular prion protein expression, which is generally well-tolerated, eliminates prion disease susceptibility entirely. Inspired by demonstrations of gene drive in caged mosquito species, we aimed to test whether a CRISPR/Cas9-based gene drive mechanism could, in principle, promote the spread of a null Prnp allele among mammalian populations. First, we showed that transient co-expression of Cas9 and Prnp-directed guide RNAs in RK13 cells generates indels within the Prnp open-reading frame, indicating that repair of Cas9-induced double-strand breaks by non-homologous end-joining had taken place. Second, we integrated a ~1.2 kb donor DNA sequence into the Prnp open-reading frame in N2a cells by homology-directed repair following Cas9-induced cleavages and confirmed that integration occurred precisely in most cases. Third, we demonstrated that electroporation of Cas9/guide RNA ribonucleoprotein complexes into fertilised mouse oocytes resulted in pups with a variety of disruptions to the Prnp open reading frame, with a new coisogenic line of Prnp-null mice obtained as part of this work. However, a technical challenge in obtaining expression of Cas9 in the male germline prevented implementation of a complete gene drive mechanism in mice.
Retraction Note: Selective inheritance of target genes from only one parent of sexually reproduced F1 progeny in Arabidopsis
22794T. Zhang, M. Mudgett, R. Rambabu, B. Abramson, X. Dai, T. P. Michael and Y. Zhao, Nature Communications, 13:3270. 2022-06-07 08:36:48.
Retraction to: Nature Communications https://doi-org.proxy-um.researchport.umd.edu/10.1038/s41467-021-24195-5, published online 22 June 2021.We retract the article cited above because genotyping results from recent experiments are not consistent with the conclusions presented in the paper.We recently genotyped a selection of F2 plants in order to identify plants to use for an introgression experiment.In the original study, we confirmed homozygosity by using a pair of oligonucleotides covering the large gene drive region in its entirety, a region that is too large to be amplified by PCR if both alleles have integrated the gene drive element. When we analyzed F2 plants using a pair of oligonucleotides targeting a smaller region of the gene drive, we found a small fragment was amplified only in about 75% of the plants. The absence of the band in the remaining F2 plants can be accounted for by a large NHEJ based deletion in one of the alleles of the F1 plants, which can result in the removal of the oligonucleotide binding sites. Thus, the F1 plants presented in the paper are not homozygous as stated in the published paper.In light of the new genotyping data that invalidate our conclusions on gene drives, we are retracting the paper. The gene targeting results of both the CRY1 lines and NPY5-GFP lines remain valid. We apologize for any inconvenience the publication of this work may have caused to the scientific community. All authors agree to the retraction.
Who decides whether to use gene drives against malaria-carrying mosquitoes?
22730T. H. Saey, ScienceNews, 2022-06-03 08:12:18.
The gene drive interferes with the insects’ ability to reproduce. It wiped out captive populations of mosquitoes in eight to 12 generations (SN: 10/27/18, p. 6) in a small lab study. In 2021, the technology worked in the large cages in Terni, Italy, too. Within as little as five to 10 years, this gene drive could be ready to test in the wild. The first experimental release could be rolled out in Burkina Faso, Mali, Ghana or Uganda. In those locations, researchers are working with a nonprofit research consortium called Target Malaria to develop the gene drive carriers along with other genetically engineered mosquitoes to fight malaria. This research is driven by the idea that every tool available must be used to fight malaria, which sickened close to 241 million people in 2020 and killed 670,000 worldwide, mostly in Africa. Children 5 years old and younger accounted for about 80 percent of the continent’s malaria deaths, the World Health Organization says. Because of malaria’s huge toll, large investments have been made to fight the disease, yielding preventive drugs, insecticide-treated bed nets and even malaria vaccines — one was recently recommended for use in sub-Saharan Africa (SN: 12/18/21 & 1/1/22, p. 32). These efforts are helping. But mosquitoes are developing resistance to insecticides, and some anti-malaria drugs may no longer work well.
Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae
22689D. A. Ellis, G. Avraam, A. Hoermann, C. A. S. Wyer, Y. X. Ong, G. K. Christophides and N. Windbichler, PLOS Genetics, 18:e1010244. 2022-06-02 14:26:57.
Author summary Gene drive is a method that allows the genetic modification of entire populations of harmful organisms. Their application to tackle invasive species, agricultural pests or insect disease vectors has been suggested. For example, they could reduce the capacity of malaria mosquitoes to transmit this deadly disease to humans by producing effector molecules inhibiting the development of the Plasmodium parasite in the mosquito vector. We describe a strategy to modularize and test multiple transgenes destined for release, and to introduce only the minimal set of modifications needed into a mosquito population. We show how some elements, once no longer needed, can be made to self-eliminate from populations and we also study how several independent gene drive traits, located in different parts of the genome, can interact and propagate at the level of mosquito cage populations.
Exploring value change
25095T. E. de Wildt and V. J. Schweizer, Prometheus, 38. 2022-06-01 10:02:19.
This article aims to explore the use of cross-impact balances (CIB) to identify scenarios of value change. The possibility of value change has received little attention in the literature on value-sensitive design (VSD). Examples of value change include the emergence of new values and changes in the relative importance of values. Value change could lead to a mismatch between values embedded in technology and the way they are currently considered in society. Such a mismatch could result in a lack of acceptability of technologies, increasing social tensions and injustices. However, methods to study value change in the VSD literature are rare. CIB is a scenario tool that can study systems characterized by feedback loops that are hard to describe mathematically. This is often the case when aiming to define values and their relationships. We demonstrate the use of CIB to identify scenarios of value change using two cases: digital voice assistants and gene drive organisms. Our findings show that CIB is helpful in building scenarios of value change, even in instances where the operationalization of values is complex. CIB also helps us to understand the mechanisms of value change and evaluate when such mechanisms occur. Finally, we find that CIB is particularly useful for social learning and explanatory modelling. CIB can therefore contribute to the design of value-sensitive technologies.
Unfolding the Next Frontier of Innovation in Malaria: The Way Forward
22699ETHealthWorld, ET Healthworld, 2022-05-30 14:53:17.
Malaria innovation is on the verge of a challenging yet exciting frontier. Therefore, to ramp up current innovatins and expand effective therapeutic and prevenitive methods, the governments, international organizations, and the private sector must work together. Additionally, malaria eradication calls for multiple innovative approaches.
Recommendations for environmental risk assessment of gene drive applications for malaria vector control
22586J. B. Connolly, J. D. Mumford, D. C. M. Glandorf, S. Hartley, O. T. Lewis, S. W. Evans, G. Turner, C. Beech, N. Sykes, M. B. Coulibaly, J. Romeis, J. L. Teem, W. Tonui, B. Lovett, A. Mankad, A. Mnzava, S. Fuchs, T. D. Hackett, W. G. Landis, J. M. Marshall, Malar J, 21:152. 2022-05-25 09:36:02.
Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.
A nickase Cas9 gene-drive system promotes super-Mendelian inheritance in Drosophila
22584V. L. Del Amo, S. S. Juste and V. M. Gantz, Cell Rep, 39:110843. 2022-05-24 09:32:51.
CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (>50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a gene-drive that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that generating 5' overhangs in the system yields efficient allelic conversion. The nickase gene-drive arrangement produces large, stereotyped deletions that are advantageous to eliminate viable animals carrying small mutations when targeting essential genes. Our nickase approach should expand the repertoire for gene-drive arrangements aimed at applications in mosquitoes and beyond.
Gene Drives: The advanced science fiction technology used to fight malaria mosquitoes explained
22563Anonymous, NewsBeezer, 2022-05-23 08:42:27.
Scientists are using the most advanced form of genetic engineering to eradicate a population of malaria-carrying mosquitoes by rendering the females infertile. Scientists introduced a lab-tweaked gene (a gene created using Gene Drive) into an organism that automatically replicates itself and targets a specific natural gene to destroy it. The potential of the gene drive was explored back in 2003 by Austin Burt, a professor at Imperial College London. Burt studied “selfish genes” that can copy themselves into a specific target DNA sequence. As research continues to develop, Burt said this technology has great potential, for example it could be used to eliminate a population of malaria-carrying mosquitoes.
The sci-fi technology tackling malarial mosquitos
22560Anonymous, The Star, 2022-05-23 08:30:39.
Environmental campaigner Liz O'Neill doesn't mince her words about gene drives - the next generation of genetic modification (GM) technology. "It is extremely worrying," says the director of UK anti-GM pressure group, GM Freeze. "To release something that has been specifically created in a laboratory in order to outfight nature, and spread without exception within wild populations, is extraordinary arrogant. "And once the genie is out of the bottle, you cannot put it back in." The way gene drives work sounds like something from a science fiction novel, but they are already being used in laboratory tests. It is complicated stuff, but here is a simple explanation.
What role can gene editing play in predator control? And are we ready to accept it?
22727K. Green, Stuff, 2022-05-16 08:07:14.
The once-forbidden concept of gene editing for predator control is back on the table after two projects receivedGovernment funding. Despite advances overseas, experts are worried research in New Zealand will never make it out of the lab, with no plans to change current restrictive laws. Appetite for gene editing has always been low among the New Zealand public. In 1999, 20,000 people protested in Auckland alone, marching down Auckland’s Queen St calling for a ban on genetically engineered crops. Gene editing joined nuclear-free as a hallmark of clean, green New Zealand. However last month, the crown entity responsible for pest control, Predator Free 2050, announced investment of $6.7 million into research projects, including $2.25m to investigate whether recent overseas advances in producing mice of only one sex could be adapted for rats, and $200,000 to explore stoat breeding genetics, and whether that could be used for control.
Bayesian network-based risk assessment of synthetic biology: Simulating CRISPR-Cas9 gene drive dynamics in invasive rodent management
22516E. A. Brown, S. R. Eikenbary and W. G. Landis, Risk Analysis, 2022-05-14 07:22:34.
Gene drive technology has been proposed to control invasive rodent populations as an alternative to rodenticides. However, this approach has not undergone risk assessment that meets criteria established by Gene Drives on the Horizon, a 2016 report by the National Academies of Sciences, Engineering, and Medicine. To conduct a risk assessment of gene drives, we employed the Bayesian network-relative risk model to calculate the risk of mouse eradication on Southeast Farallon Island using a CRISPR-Cas9 homing gene drive construct. We modified and implemented the R-based model "MGDrivE" to simulate and compare 60 management strategies for gene drive rodent management. These scenarios spanned four gene drive mouse release schemes, three gene drive homing rates, three levels of supplemental rodenticide dose, and two timings of rodenticide application relative to gene drive release. Simulation results showed that applying a supplemental rodenticide simultaneously with gene drive mouse deployment resulted in faster eradication of the island mouse population. Gene drive homing rate had the highest influence on the overall probability of successful eradication, as increased gene drive accuracy reduces the likelihood of mice developing resistance to the CRISPR-Cas9 homing mechanism.
Aquatic invasive species specialists’ perceptions on the importance of genetic tools and concepts to inform management
22482T. A. Bernos, K. M. Jeffries and N. E. Mandrak, Biological Invasions, 24:1863-1879. 2022-05-14 07:09:36.
Perceptions related to the importance of genetic research influence the mobilization of genetic tools and concepts to inform conservation actions. Research characteristics, stakeholders’ perspectives, knowledge, and social linkages with geneticists influence the outcome of genetic information for management practices. We surveyed a broad range of aquatic invasive species (AIS) specialists whose opinions, perspectives, and decisions influence AIS decision-making. We assessed perceptions related to the importance of genetic tools and concepts, as well as the appropriateness of genetic biocontrol, and tested whether their expertise, background, and experience influenced perceptions in a predictable way. While perceptions towards genetic tools and concepts were generally heterogeneous, there was a high consensus (84%) related to the importance of eDNA. Most predictors were weakly correlated with importance ratings. Specialists’ genetic knowledge was the strongest predictor of higher importance ratings: the odds of AIS specialists giving higher ratings increased by up to 1.5-fold with increasing genetic knowledge. When evaluating the appropriateness of genetic biocontrol, level of support was lower for approaches based on gene editing (58%) than those relying on traditional hatchery techniques (70%). Support for gene editing varied by geographic location and with specialists’ knowledge of genetics and AIS management. These findings suggest that perceptions towards genetic research vary between genetic tools and concepts and are shaped by the interplay of individual’s values, expertise, experience, and background. To collaborate more effectively, genetic scientists must understand the extent of genetic knowledge of their AIS management partners and recognize that their conceptions of the conservation genetics research-practice space may vary.
Intronic gRNAs for the Construction of Minimal Gene Drive Systems
22478A. Nash, P. Capriotti, A. Hoermann, P. A. Papathanos and N. Windbichler, Frontiers in Bioengineering and Biotechnology, 10. 2022-05-12 07:00:08.
Gene drives are promising tools for the genetic control of insect vector or pest populations. CRISPR-based gene drives are generally highly complex synthetic constructs consisting of multiple transgenes and their respective regulatory elements. This complicates the generation of new gene drives and the testing of the behavior of their constituent functional modules. Here, we explored the minimal genetic components needed to constitute autonomous gene drives in Drosophila melanogaster. We first designed intronic gRNAs that can be located directly within coding transgene sequences and tested their functions in cell lines. We then integrated a Cas9 open reading frame hosting such an intronic gRNA within the Drosophila rcd-1r locus that drives the expression in the male and female germlines. We showed that upon removal of the fluorescent transformation marker, the rcd-1rd allele supports efficient gene drive. We assessed the propensity of this driver, designed to be neutral with regards to fitness and host gene function, to propagate in caged fly populations. Because of their simplicity, such integral gene drives could enable the modularization of drive and effector functions. We also discussed the possible biosafety implications of minimal and possibly recoded gene drives.
Importation of the non gene drive genetically modified male bias mosquito strain into Burkina Faso
22496A. Diabate, Target Malaria, 2022-05-11 07:37:11.
On March 16 and 21, the team at the Institut de Recherche en Sciences de la Santé (IRSS), Target Malaria’s partner institution in Burkina Faso, received packages containing live genetically modified mosquito eggs from Italy. The National Biosafety Agency (ANB) officers were at the airport to inspect the packages. The eggs are of non gene drive genetically modified male bias mosquitoes. It is another strain of genetically modified mosquitoes, compared to the sterile male strain imported in 2016 and released in 2019. This male bias strain does not carry the gene drive technology. The mosquito is fertile and it is genetically modified to produce mainly male offspring (up to 95% in the laboratory). The male bias strain is not a vector control tool. The purpose of this phase is to understand this new fertile strain, develop capacity, train Target Malaria teams and engage with regulatory authorities and stakeholders.
Self-Deleting Genes Could Control Mosquitoes And Prevent Vector-Borne Diseases
22493A. Russell, Texas AM TODAY, 2022-05-11 07:33:02.
Texas A&M AgriLife Research scientists are testing a technology to make temporary genetic modifications in mosquitoes that self-delete over time. The mechanism to make temporary genetic changes could be important for scientists hoping to modify mosquitoes in ways that help manage populations and prevent vector-borne diseases like West Nile virus without permanently altering wild populations’ genetic makeup. An article detailing their test results is published in Proceedings of the National Academy of Sciences’ PNAS Nexus. The authors, Zach Adelman and Kevin Myles, both professors in the Texas A&M University College of Agriculture and Life Sciences Department of Entomology, describe a method for programming the removal of edited genes within populations of mosquitoes over multiple generations. The method is a first step toward building safeguards for genetic modifications developed to control populations of mosquitoes and the vector-borne diseases they carry. The idea is to test proposed changes without making the changes permanent and without the risk of transmitting them to wild populations, Adelman said.
Lessons learned from the introduction of genetically engineered crops: relevance to gene drive deployment in Africa
22491H. Quemada, Transgenic Res, 2022-05-11 07:27:12.
The application of gene drives to achieve public health goals, such as the suppression of Anopheles gambiae populations, or altering their ability to sustain Plasmodium spp. infections, has received much attention from researchers. If successful, this genetic tool can contribute greatly to the wellbeing of people in regions severely affected by malaria. However, engineered gene drives are a product of genetic engineering, and the experience to date, gained through the deployment of genetically engineered (GE) crops, is that GE technology has had difficulty receiving public acceptance in Africa, a key region for the deployment of gene drives. The history of GE crop deployment in this region provides good lessons for the deployment of gene drives as well
Self-eliminating Genes Tested on Disease-carrying Mosquitoes
22292M. Taylor, Laboratory Equipment, 2022-05-09 08:25:47.
There’s good reason why CRISPR-Cas9 gene editing is not allowed at the germline. While international commissions are working hard to make this a possibility, potential unknown effects further down the ancestry line raise concerns about the process. The insect equivalent of this—gene drive transgene research—hasn’t been a cause of much concern for researchers working on genetic control of vector populations, especially disease-carrying mosquitoes. Scientists from Texas A&M, however, think the potential affects should be always be considered and have now devised a technology to make all genetic modifications in mosquitoes temporary—until a time when adequate testing ensures safety. Zach Adelman, author of a new paper on the research and a professor at Texas A&M, says many of today’s insect genetic control strategies are based on highly invasive, self-propagating transgenes that can rapidly spread the trait into other populations of mosquitoes. Adelman’s method, however, allows proposed genetic changes to be tested on a temporary basis—without the risk of transmitting them to wild populations. The temporary genetic modifications self-delete over multiple generations of mosquitoes.
Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles
22286A. L. Bishop, V. López Del Amo, E. M. Okamoto, Z. Bodai, A. C. Komor and V. M. Gantz, Nat Commun, 13:2595. 2022-05-09 08:10:07.
Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the drive-induced DNA break is repaired by error-prone pathways, which creates mutations that disrupt the gRNA recognition sequence and prevent further gene-drive propagation. Here, we attempt to counteract this by encoding additional gRNAs that target the most commonly generated resistance alleles into the gene drive, allowing a second opportunity at gene-drive conversion. Our presented "double-tap" strategy improved drive efficiency by recycling resistance alleles. The double-tap drive also efficiently spreads in caged populations, outperforming the control drive. Overall, this double-tap strategy can be readily implemented in any CRISPR-based gene drive to improve performance, and similar approaches could benefit other systems suffering from low HDR frequencies, such as mammalian cells or mouse germline transformations.
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models
22288Y. Liu, W. Teo, H. Yang and J. Champer, bioRxiv, 2022.05.08.491087. 2022-05-08 08:15:29.
Suppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population will be unable to reproduce above the replacement level and could be eliminated. CRISPR suppression drives based on the homing mechanism have already seen success in the laboratory, particularly in malaria mosquitoes. However, several models predict that the use of these drives in realistic populations with spatial structure may not achieve complete success. This is due to the ability of wild-type individuals to escape the drive and reach empty areas with reduced competition, allowing them to achieve high reproductive success and leading to extinction-recolonization cycles across the landscape. Here, we extend our continuous space gene drive framework to include two competing species or predator-prey species pairs. We find in both discrete-generation and mosquito-specific models that the presence of a competing species or predator can greatly facilitate drive-based suppression, even for drives with modest efficiency. However, the presence of a competing species also substantially increases the frequency of outcomes in which the drive is lost before suppression is achieved. These results are robust in models with seasonal population fluctuations. We also found that suppression can be somewhat more difficult if targeting a predator with strong predator-prey interactions. Our results illustrate the difficulty of predicting outcomes of interventions that could substantially affect the populations of interacting species in complex ecosystems. However, our results are also potentially promising for the prospects of less powerful gene drives in achieving successful elimination of target pest populations.Competing Interest StatementThe authors have declared no competing interest.
The principles driving gene drives for conservation
22295S. Hartley, R. Taitingfong and P. Fidelman, Environmental Science and Policy, 135:36-45. 2022-05-04 08:30:40.
Gene drive technology is an emerging biotechnology with the potential to address some of the most intractable global biodiversity conservation issues. Scientists are exploring potential gene drive applications for managing invasive species and building resilience in keystone species threatened by climate change. The possibility to use gene drive for these conservation purposes has triggered significant interest in how to govern its development and eventual applications. This includes a plethora of documents prescribing governance principles, which can be a sensible response to the governance gap created by emerging technologies and help shore up legitimacy. We conducted qualitative documentary analysis to examine the range and substance of principles emerging in the governance of conservation gene drive. Such analysis aimed to better understand the aspirations guiding these applications and how scientists and other experts imagine their responsibility in this field. We found a collection of recommendations and prescriptions that could be organised into a set of seven emerging principles intended to shape the governance of gene drive in conservation: broad and empowered engagement; public acceptance; decision-making informed by broad ranging considerations, state and international collaboration; ethical frameworks; diverse expertise; and responsible self-regulation by developers. We lay bare these emergent principles, analyzing the way in which they are valued, prioritized, and their strengths and weaknesses. By identifying these prescriptive principles, stakeholders can further interrogate their merits and shortcomings and identify more concrete ways that governance frameworks might embody them.
New weapons to fight malaria transmission: A historical view
22487W. Huang, S.-J. Cha and M. Jacobs-Lorena, Entomological Research, 2022-05-02 07:19:32.
The stagnation of our fight against malaria in recent years, mainly due to the development of mosquito insecticide resistance, argues for the urgent development of new weapons. The dramatic evolution of molecular tools in the last few decades led to a better understanding of parasite?mosquito interactions and coalesced in the development of novel tools namely, mosquito transgenesis and paratransgenesis. Here we provide a historical view of the development of these new tools and point to some remaining challenges for their implementation in the field.
GeneConvene Global Collaborative Webinar Series | Demystifying the Convention on Biological Diversity – Seven Videos
21940Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2022-04-28 12:39:49.
The Convention on Biological Diversity (CBD) is an international agreement aimed at providing the legal framework for country cooperation to conserve biodiversity, while also enabling its sustainable use, and providing for fair and equitable sharing of the benefits derived from that use. It became effective in 1993 when the first 30 countries signed it, but now has 196 parties. Biotechnology figures prominently in this agreement, since one of its major goal is to "promote and advance priority access on a fair and equitable basis by Contracting Parties, especially developing countries, to the results and benefits arising from biotechnologies." The CBD provides the basis for regulations on biotechnologies, particularly genetically engineered organisms (including gene drive organisms). While the convention, and its subsidiary agreements, have a significant impact on the regulatory environment within which synthetic gene drive research takes place, the procedures and decision-making processes connected with the CBD are often not transparent to researchers and others who do not closely follow the proceedings.
Engineering a self-eliminating transgene in the yellow fever mosquito, Aedes aegypti
21920K. Chae, C. Dawson, C. Valentin, B. Contreras, J. Zapletal, K. M. Myles and Z. N. Adelman, PNAS Nexus, 2022-04-28 08:54:37.
Promising genetics-based approaches are being developed to reduce or prevent the transmission of mosquito-vectored diseases. Less clear is how such transgenes can be removed from the environment, a concern that is particularly relevant for highly invasive gene drive transgenes. Here, we lay the groundwork for a transgene removal system based on single-strand annealing (SSA), a eukaryotic DNA repair mechanism. An SSA-based rescuer strain (kmoRG) was engineered to have direct repeat sequences (DRs) in the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene flanking the intervening transgenic cargo genes, DsRED and EGFP. Targeted induction of DNA double-strand breaks (DSBs) in the DsRED transgene successfully triggered complete elimination of the entire cargo from the kmoRG strain, restoring the wild-type kmo gene and thereby normal eye pigmentation. Our work establishes the framework for strategies to remove transgene sequences during the evaluation and testing of modified strains for genetics-based mosquito control.
The Financialisation of Malaria in Africa: Burkina Faso, rogue capital & GM/gene drive mosquitoes
22066S. Mentz-Lagrange and S. Swanepoel, African Centre for Biodiversity, 2022-04-28 07:02:28.
This paper seeks to understand the financialisation of malaria as a vehicle for rogue capital in a context of a weakened state (through capture, corruption and coups) and the power that limits effective interventions. It shows how malaria, along with other diseases, is increasingly financialised – financial markets, institutions, actors and motives play a pivotal role in disease response. Country and donor funds are invested into research and development non-profit organisations, for example, that partner with market actors (such as pharmaceutical companies) to bring the product to market. Patents are sought and royalties procured from the sale of the product to country governments. These royalties are then accumulated by the research and development company, using vehicles such as endowment funds, for example. It show cases Burkina Faso as a real-world example of how rogue capital can enter a country and experiment with patented products, with impunity and no fear of accountability. It also illustrates how both historical and modern factors create conducive conditions for philanthrocapitalists such as the Bill and Melinda Gates Foundation and the companies they fund, to exploit Africa as a living laboratory. The outcomes of risky experimental research such as genetically modified (GM) and gene drive mosquitoes is not yet known. What is known is that it is Africans who bear the consequences – not the owners of the technologies foisted on the continent.
Self-eliminating genes tested on mosquitoes
21924A. Russell, AGRILIFE Today, 2022-04-27 09:13:46.
Texas A&M AgriLife Research scientists have tested a technology to make temporary genetic modifications in mosquitoes. The modifications self-delete over time. Texas A&M AgriLife Research scientists published an article detailing a mechanism to make temporary genetic alterations to mosquitoes. The mechanism to make temporary genetic changes could be important for scientists hoping to modify mosquitoes in ways that help manage populations and prevent vector-borne diseases like West Nile virus without permanently altering wild populations’ genetic makeup.
A New Approach to Develop Resistant Cultivars Against the Plant Pathogens: CRISPR Drives
21915M. I. Tek and K. Budak, Frontiers in Plant Science, 13. 2022-04-27 08:43:50.
CRISPR drive is a recent and robust tool that allows durable genetic manipulation of the pest population like human disease vectors such as malaria vector mosquitos. In recent years, it has been suggested that CRISPR drives can also be used to control plant diseases, pests, and weeds. However, using a CRISPR drive in Arabidopsis for the first time in 2021 has been shown to use this technology in plant breeding to obtain homozygous parental lines. This perspective has proposed using CRISPR drive to develop pathogen-resistant cultivars by disrupting the susceptibility gene (S). In the breeding program, CRISPR is used to create S-gene mutations in two parental lines of hybrid cultivars. However, CRISPR must be reapplied or long-term backcrossed for the parental line to obtain homozygous S-mutant cultivars. When a parental line crosses with different parental lines to develop new hybrids, heterozygous S-mutations could not resist in hybrid against the pathogen. CRISPR drives are theoretically valid to develop homozygous S-mutant plants against pathogens by only routine pollination after CRISPR drive transformation to just one parental line. This way, breeders could use this parental line in different crossing combinations without reapplying the genome-editing technique or backcrossing. Moreover, CRISPR drive also could allow the development of marker-free resistant cultivars with modifications on the drive cassette.
Recent advancements in CRISPR/Cas technology for accelerated crop improvement
21827D. Das, D. L. Singha, R. R. Paswan, N. Chowdhury, M. Sharma, P. S. Reddy and C. Chikkaputtaiah, Planta, 255:109. 2022-04-25 09:34:49.
The likelihood of reduced agricultural production due to highly turbulent climatic conditions increases as the global population expands. The second paradigm of stress-resilient crops with enhanced tolerance and increased productivity against various stresses is paramount to support global production and consumption equilibrium. Although traditional breeding approaches have substantially increased crop production and yield, effective strategies are anticipated to restore crop productivity even further in meeting the world’s increasing food demands. CRISPR/Cas, which originated in prokaryotes, has surfaced as a coveted genome editing tool in recent decades, reshaping plant molecular biology in unprecedented ways and paving the way for engineering stress-tolerant crops. CRISPR/Cas is distinguished by its efficiency, high target specificity, and modularity, enables precise genetic modification of crop plants, allowing for the creation of allelic variations in the germplasm and the development of novel and more productive agricultural practices. Additionally, a slew of advanced biotechnologies premised on the CRISPR/Cas methodologies have augmented fundamental research and plant synthetic biology toolkits. Here, we describe gene editing tools, including CRISPR/Cas and its imitative tools, such as base and prime editing, multiplex genome editing, chromosome engineering followed by their implications in crop genetic improvement. Further, we comprehensively discuss the latest developments of CRISPR/Cas technology including CRISPR-mediated gene drive, tissue-specific genome editing, dCas9 mediated epigenetic modification and programmed self-elimination of transgenes in plants. Finally, we highlight the applicability and scope of advanced CRISPR-based techniques in crop genetic improvement.
Biotechnological Road Map for Innovative Weed Management
22450A. C. S. Wong, K. Massel, Y. Lam, J. Hintzsche and B. S. Chauhan, Frontiers in Plant Science, 13. 2022-04-25 09:27:40.
In most agriculture farmlands, weed management is predominantly reliant on integrated weed management (IWM) strategies, such as herbicide application. However, the overuse and misuse of herbicides, coupled with the lack of novel active ingredients, has resulted in the uptrend of herbicide-resistant weeds globally. Moreover, weedy traits that contribute to weed seed bank persistence further exacerbate the challenges in weed management. Despite ongoing efforts in identifying and improving current weed management processes, the pressing need for novel control techniques in agricultural weed management should not be overlooked. The advent of CRISPR/Cas9 gene-editing systems, coupled with the recent advances in “omics” and cheaper sequencing technologies, has brought into focus the potential of managing weeds in farmlands through direct genetic control approaches, but could be achieved stably or transiently. These approaches encompass a range of technologies that could potentially manipulate expression of key genes in weeds to reduce its fitness and competitiveness, or, by altering the crop to improve its competitiveness or herbicide tolerance. The push for reducing or circumventing the use of chemicals in farmlands has provided an added incentive to develop practical and feasible molecular approaches for weed management, although there are significant technical, practical, and regulatory challenges for utilizing these prospective molecular technologies in weed management.
Genetically altered mosquitoes to close gaps in malaria fight
22248M. Murigi, People Daily, 2022-04-25 09:00:48.
In 2020, nearly 6.9 million cases of malaria and about 742 deaths were confirmed in Kenya according to the Kenya Malaria Indicator Survey (KMIS) 2020. Although the number of reported infections declined from 10.9 million in 2018, the disease is still one of the main health issues in the country despite being a largely preventable and treatable disease. Kenya is not the only country suffering from the burden of this life-threatening disease. According to World Health Organisation (WHO) latest world malaria report, there were an estimated 241 million malaria cases and 627,000 malaria deaths worldwide in 2020. This represents about 14 million more cases in 2020 compared to 2019, and 69,000 more deaths. The high number of malaria cases continues to be registered even though several efforts have been put in place towards malaria eradication. It is for this reason scientists and researchers are assessing the use of new tools to edit the genes of malaria-transmitting mosquitoes as they try to come up with a long-lasting solution towards control and elimination of this disease. “The war against malaria has been ongoing for decades. It has led to the development of several interventions strategies, such as antimalarial drugs, insecticide-treated nets, and vaccines among others. However, despite all the interventions, the disease has not been eradicated because there are increased cases of insecticide resistance in mosquitoes, which pose a significant public health concern,” says Dr Willy Kiprotich Tonui, EBS, the Chairman and Executive Director at the Environmental Health Safety (EHS) Consultancy Limited who also doubles up as the Founder and Head of Secretariat to African Genetic Biocontrol Consortium.
Role of CRISPR Technology in Gene Editing of Emerging and Re-emerging Vector Borne Disease
21811K. K. Mahto, P. Prasad, M. Kumar, H. Dubey and A. Ranjan, Recent Advances in Pathogen Interactions, Immunity, and Vector Control Strategies, 2022-04-23 05:49:18.
Vector borne diseases are rampant across the world. Due to spread and estab-lishment of vector species in different geographical areas, vector adaptation and resistance towards many insecticides the only option left is vector control for vari-ous vector borne diseases. Recent advancement in the field of genome editing have provided a variety of tools like, CRISPR, a novel genome editing techniques which can be applied for the control and prevention of many deadly diseases like dengue, chikungunya, filariasis, Japanese encephalitis and Zika. The present chapter is aimed to discuss the recent advancement in genome editing tools such as, their applica-tion, challenges, and limitations in vector control. Additionally, this chapter would potentially be advantageous to understand the hurdles, knowledge gaps in eliminating vector borne disease.
Propagation of seminal toxins through binary expression gene drives could suppress populations
21691J. Hurtado, S. Revale and L. M. Matzkin, Scientific Reports, 12:6332. 2022-04-15 08:22:57.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.
New frontiers in vector control
21717WHO, World Health Organization, 2022-04-11 09:17:11.
Ever since Sir Ronald Ross discovered malaria parasites in an Anopheles mosquito in 1897, controlling insect vectors has played an increasingly important role in reducing the burden of the disease. For decades after World War II, indoor residual spraying (IRS) with insecticides was the only weapon against mosquitoes and proved a blunt and reasonably effective instrument for protecting people inside their homes. Then, beginning in the early 2000s, insecticide-treated nets (ITNs) became a new addition to countries’ vector control strategies. Thanks, in part, to the wide deployment of these 2 WHO-recommended interventions, the world made remarkable gains against malaria in the period 2000–2015. But progress plateaued, and this troubling slowdown was exacerbated by COVID-19. According to WHO’s latest World malaria report, 2020 saw a rise in the global burden of malaria, with an estimated 627 000 deaths and 241 million new cases of the disease. Getting back on track, and meeting WHO’s targets of a 90% reduction in malaria case incidence and mortality rates by 2030, will require renewed global attention, increased funding, and continued research and development of new interventions, among other actions. In the field vector control, researchers are working on several innovations that aim to enhance efforts to combat the disease.
Explainer: The Gene Drive Technology
21701P. Shah, CRISPR Medicine News, 2022-04-11 08:45:54.
Gene drives are genetic elements that can quickly spread through populations and have nearly a 100% chance of passing the genes they carry to the next generation. Synthetic gene drive is a technology of genetic engineering through which certain desired traits can be introduced to almost all individuals in a population. Researchers can either eliminate a species or alter the genetic makeup of living organisms through gene drive technology.
A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles
22572E. Yang, M. Metzloff, A. M. Langmuller, X. J. Xu, A. G. Clark, P. W. Messer and J. Champer, G3-Genes Genomes Genetics, 13. 2022-04-08 09:02:04.
Gene drives are engineered alleles that can bias inheritance in their favor, allowing them to spread throughout a population. They could potentially be used to modify or suppress pest populations, such as mosquitoes that spread diseases. CRISPR/Cas9 homing drives, which copy themselves by homology-directed repair in drive/wild-type heterozygotes, are a powerful form of gene drive, but they are vulnerable to resistance alleles that preserve the function of their target gene. Such resistance alleles can prevent successful population suppression. Here, we constructed a homing suppression drive in Drosophila melanogaster that utilized multiplexed gRNAs to inhibit the formation of functional resistance alleles in its female fertility target gene. The selected gRNA target sites were close together, preventing reduction in drive conversion efficiency. The construct reached a moderate equilibrium frequency in cage populations without apparent formation of resistance alleles. However, a moderate fitness cost prevented elimination of the cage population, showing the importance of using highly efficient drives in a suppression strategy, even if resistance can be addressed. Nevertheless, our results experimentally demonstrate the viability of the multiplexed gRNAs strategy in homing suppression gene drives.
Cas9-mediated maternal-effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae
21663R. Carballar-Lejarazú, T. Tushar, T. B. Pham and A. A. James, Genetics, 2022-04-07 15:16:08.
CRISPR/Cas9 technologies are important tools for the development of gene-drive systems to modify mosquito vector populations to control the transmission of pathogens that cause diseases such as malaria. However, one of the challenges for current Cas9-based drive systems is their ability to produce drive-resistant alleles resulting from insertions and deletions (indels) caused principally by nonhomologous end-joining following chromosome cleavage. Rapid increases in the frequency of such alleles may impair gene-drive dynamics. We explored the generation of indels in the germline and somatic cells in female gene-drive lineages using a series of selective crosses between a gene-drive line, AgNosCd-1, and wild-type mosquitoes. We find that potential drive-resistant mutant alleles are generated largely during embryonic development, most likely caused by deposition of the Cas9 endonuclease and guide RNAs in oocytes and resulting embryos by homozygous and hemizygous gene-drive mothers.
A multi-disciplinary approach for a building common understanding of genetic engineering for malaria control in Burkina Faso
21637L. Pare Toe, N. Barry, A. D. Ky, S. Kekele, W. I. Meda, K. Bayala, et al., Humanities and Social Sciences Communications, 9. 2022-04-05 08:18:54.
Genetic engineering is a complex topic, even for scientists working in other areas, and even more so for those who lack a formal scientific training. To help gene specialists and affected communities talk with one another, international guidance documents have been published that promote dialogue and exchanges. The current paper explores collaboration among scientists of different disciplines as well as between scientists, the local communities, mediated by theatre actors to develop a conversation about Target Malaria’s work on genetic technologies to modify mosquitoes for malaria elimination in Burkina Faso. It focuses on the co-construction of meaning of key scientific concepts with a view to fostering productive collaboration between scientists and the local community. The community provided feedback on what was shared with them regarding the science being developed in the lab and in the field, which in turn informed aspects of the research itself, and the nature of the collaboration between the scientists and the local community.
Governing Gene Drive Technologies: A Qualitative Interview Study
23410N. de Graeff, K. R. Jongsma, J. E. Lunshof and A. L. Bredenoord, AJOB Empirical Bioethics, 13:107-124. 2022-04-04 12:10:12.
Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth.Methods A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically.Results Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment.Conclusions The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations.
Expanding the flexibility of genome editing approaches for population control of the malaria mosquito
22226N. Kranjc, Imperial College London-PhD, 2022-04-01 15:50:55.
Discovery and adaptation of CRISPR-Cas systems for genome editing have allowed us to gain an efficient and yet simple tool for genetic manipulation in various fields of molecular biology and biotechnology. One of the most promising applications is the use of CRISPR-Cas9 endonuclease for gene drive systems as a population control strategy for various insect pests of medical and agricultural importance. Use of CRISPR-Cas9 endonuclease in gene drive applications has shown great promise in the laboratory, particularly for the control of Anopheles gambiae, the major vector of malaria. However, the performance of such gene drives can be limited by the range of available target sequences and by a propensity of existing endonuclease formulations to generate resistant mutations that hinder the gene drive’s efficiency. To expand the flexibility of gene drive systems, computational analysis was performed to identify additional Cas9 orthologs and their specificities that could usefully augment the targeting range of endonuclease-based gene drives. Two alternative variants of CRISPR-Cas endonucleases found in the bacterial species Lactobacillus rhamnosus and Bacteroides fragilis were assessed for their potential to expand the targeting space in the genome Anopheles gambiae. In addition, a computational tool was developed that evaluates neighbouring sequences to the target site to measure both its likely functional constraint and its likely propensity for DNA repair that could generate in-frame alleles. Using this approach we were able to generate a prioritized list of Anopheles gambiae target sites for gene drive applications that are less likely to be compromised by resistant alleles.
Toward a CRISPR-Cas9-Based Gene Drive in the Diamondback Moth Plutella xylostella
24426X. Xu, T. Harvey-Samuel, H. A. Siddiqui, J. X. D. Ang, M. E. Anderson, C. M. Reitmayer, E. Lovett, P. T. Leftwich, M. You and L. Alphey, The CRISPR Journal, 5:224-236. 2022-04-01 10:25:39.
Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipteran insects, yeast, and mice for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. Here, we used endogenous regulatory elements to drive Cas9 and single guide RNA (sgRNA) expression in the diamondback moth (DBM), Plutella xylostella, and test the first split gene drive system in a lepidopteran. The DBM is an economically important global agriculture pest of cruciferous crops and has developed severe resistance to various insecticides, making it a prime candidate for such novel control strategy development. A very high level of somatic editing was observed in Cas9/sgRNA transheterozygotes, although no significant homing was revealed in the subsequent generation. Although heritable Cas9-medated germline cleavage as well as maternal and paternal Cas9 deposition were observed, rates were far lower than for somatic cleavage events, indicating robust somatic but limited germline activity of Cas9/sgRNA under the control of selected regulatory elements. Our results provide valuable experience, paving the way for future construction of gene drives or other Cas9-based genetic control strategies in DBM and other lepidopterans.
UC Davis — Malaria Gene Drive Feasibility Analysis
21563Good Ventures, Good Ventures, 2022-03-31 12:24:36.
Open Philanthropy recommended a grant of $10,248,967 over three years to UC Davis to support subsequent stages of a feasibility analysis of a potential test of gene drives for malaria control on the adjoining West African islands of São Tomé and Príncipe. The work, led by Dr. Greg Lanzaro and colleagues, will focus on a potential gene drive application that would reduce or inhibit the ability of mosquitoes to transmit the malarial parasite, without impacting the size of the mosquito population on the islands. As part of the preliminary feasibility analysis, which Open Philanthropy supported in February 2020, Dr. Lanzaro’s team developed working relationships with local communities, established an ethics advisory board, developed a communication plan, and conducted appropriate safety tests.
UC San Diego Biology Lab Receives $1.4M Grant to Fight Malaria Spread
21561E. Dameron, UC San Diego News Center, 2022-03-30 12:17:33.
Scientists at the University of California San Diego are hard at work on new genetic technologies intended for use in curbing mosquito populations, fighting the spread of malaria and mitigating the hazards associated with the deployment of gene-editing systems in the wild. That work is now being bolstered by a $1.4 million grant from the Bill & Melinda Gates Foundation. “My lab, historically, was a fruit fly lab,” said Ethan Bier, distinguished professor of developmental biology at UC San Diego and science director for the Tata Institute for Genetics and Society. “About five years ago in collaboration with the laboratory of Anthony James at UC Irvine, we started transferring some of our genetic strategies into mosquitoes. We’re very fortunate that the Gates Foundation is supporting the continuation of that work.”
Prescribing engagement in environmental risk assessment for gene drive technology
21689S. Hartley, A. Kokotovich and C. McCalman, Regulation and Governance, 2022-03-29 08:17:38.
Abstract Gene drive technology is a nascent biotechnology with the potential to purposefully alter or eliminate a species. There have been broad calls for engagement to inform gene drive governance. Over the past seven years, the gene drive community has been developing risk assessment guidelines to determine what form future gene drive risk assessments take, including whether and how they involve engagement. To explore who is developing these guidelines and how engagement in risk assessment is being prescribed, we conduct a document analysis of gene drive risk assessment guideline documents from 2014 to 2020. We found that a narrow set of organizations have developed 10 key guideline documents and that with only one exception the documents prescribe a narrow, vague, or completely absent role for engagement in gene drive risk assessment. Without substantively prescribed engagement in guidelines, the relevance, rigor, and trustworthiness of gene drive risk assessment and governance will suffer.
Finding the strongest gene drive: Simulations reveal unexpected performance differences between Anopheles homing suppression drive candidates
21566S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer, bioRxiv, 2022.03.28.486009. 2022-03-28 12:29:28.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter driving CRISPR/Cas9, was able to eliminate a cage population of mosquitoes. A second version, purportedly improved upon the first by incorporating an X-shredder element (which biases inheritance towards male offspring), was similarly successful. Here, we re-analyze the data of each of these gene drives and suggest an alternative interpretation of their performance. We assess each suppression drive within an individual-based simulation framework that models mosquito population dynamics in continuous space. We find that the combined homing/X-shredder drive is actually less effective at population suppression within the context of our mosquito population model. In particular, the combined drive often fails to completely suppress the population, instead resulting in an unstable equilibrium between drive and wild-type alleles. By contrast, otherwise similar drives based on the nos promoter may prove to be more promising candidates for future development due to potentially superior performance.Competing Interest StatementThe authors have declared no competing interest.
Opening up, closing down, or leaving ajar? How applications are used in engaging with publics about gene drive
21287A. W. Russell, A. Stelmach, S. Hartley, L. Carter and S. Raman, Journal of Responsible Innovation, 2022-03-22 12:32:50.
Public engagement and responsible innovation are strongly emphasised in gene drive research, together with the goal of addressing societal challenges, notably, malaria and environmental conservation. We aim to explore whether public engagement is used to ‘open up' or ‘close down' opportunities to shape gene drive research. Drawing on interviews with gene drive developers and stakeholders, we investigate how the public communication of gene drive is conceived. We find that traditional closing-down tendencies remain, but that there are new and encouraging opening-up approaches. Consistent with responsible innovation thinking, these frame gene drive as multifaceted, context-dependent and requiring deeper deliberation. We also identify a third ‘leaving ajar’ approach that seeks to engage with and respond to local communities and modify technological applications to be more acceptable. Innovation system constraints may well temper current aspirations to open up; framing public conversations around understandings of public good could offer a way forward.
CRISPR-mediated knockout of cardinal and cinnabar eye pigmentation genes in the western tarnished plant bug
21243C. C. Heu, R. J. Gross, K. P. Le, D. M. LeRoy, B. Fan, J. J. Hull, C. S. Brent and J. A. Fabrick, Scientific Reports, 12. 2022-03-22 06:19:14.
The western tarnished plant bug, Lygus hesperus, is a key hemipteran pest of numerous agricultural, horticultural, and industrial crops in the western United States and Mexico. A lack of genetic tools in L. hesperus hinders progress in functional genomics and in developing innovative pest control methods such as gene drive. Here, using RNA interference (RNAi) against cardinal (LhCd), cinnabar (LhCn), and white (LhW), we showed that knockdown of LhW was lethal to developing embryos, while knockdown of LhCd or LhCn produced bright red eye phenotypes, in contrast to wild-type brown eyes. We further used CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated) genome editing to generate germline knockouts of both LhCd (Card) and LhCn (Cinn), producing separate strains of L. hesperus characterized by mutant eye phenotypes. Although the cardinal knockout strain Card exhibited a gradual darkening of the eyes to brown typical of the wild-type line later in nymphal development, we observed bright red eyes throughout all life stages in the cinnabar knockout strain Cinn, making it a viable marker for tracking gene editing in L. hesperus. These results provide evidence that CRISPR/Cas9 gene editing functions in L. hesperus and that eye pigmentation genes are useful for tracking the successful genetic manipulation of this insect.
Symbionts and gene drive: two strategies to combat vector-borne disease
21029G.-H. Wang, J. Du, C. Y. Chu, M. Madhav, G. L. Hughes and J. Champer, Trends in Genetics, 2022-03-18 07:56:11.
Mosquitoes bring global health problems by transmitting parasites and viruses such as malaria and dengue. Unfortunately, current insecticide-based control strategies are only moderately effective because of high cost and resistance. Thus, scalable, sustainable, and cost-effective strategies are needed for mosquito-borne disease control. Symbiont-based and genome engineering-based approaches provide new tools that show promise for meeting these criteria, enabling modification or suppression approaches. Symbiotic bacteria like Wolbachia are maternally inherited and manipulate mosquito host reproduction to enhance their vertical transmission. Genome engineering-based gene drive methods, in which mosquitoes are genetically altered to spread drive alleles throughout wild populations, are also proving to be a potentially powerful approach in the laboratory. Here, we review the latest developments in both symbionts and gene drive-based methods. We describe some notable similarities, as well as distinctions and obstacles, relating to these promising technologies.
The power of gene editing
20973The Economist, The Economist, 2022-03-17 07:27:42.
Technologies such as genetic modification and ‘CRISPR’ will cure hereditary diseases, produce disease-resistant crops and enable the breeding of malaria-free mosquitos. But advances bring ethical and practical dilemmas. Genetically modified food is banned in the EU, and doctors worry that screening for genetic diseases may pave the way for more controversial uses, such as creating so-called designer babies. This film looks at the risks and rewards of gene editing.
Modelling homing suppression gene drive in haplodiploid organisms
21016Y. Liu and J. Champer, bioRxiv, 2021.10.12.464047. 2022-03-15 06:38:01.
Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some potential target species are haplodiploid, in which males develop from unfertilized eggs and thus have only one copy of each chromosome. This prevents drive conversion, a substantial disadvantage compared to diploids where drive conversion can take place in both sexes. Here, we study homing suppression gene drives in haplodiploids and find that a drive targeting a female fertility gene could still be successful. However, such drives are less powerful than in diploids and suffer more from functional resistance alleles. They are substantially more vulnerable to high resistance allele formation in the embryo due to maternally deposited Cas9 and gRNA and also to somatic cleavage activity. Examining spatial models where organisms move over a continuous landscape, we find that haplodiploid suppression drives surprisingly perform nearly as well as in diploids, possibly due to their ability to spread further before inducing strong suppression. Together, these results indicate that gene drive can potentially be used to effectively suppress haplodiploid populations.Competing Interest StatementThe authors have declared no competing interest.
California Residents’ Perceptions of Gene Drive Systems to Control Mosquito-Borne Disease
20593C. E. Schairer, C. Triplett, O. S. Akbari and C. S. Bloss, Frontiers in Bioengineering and Biotechnology, 10. 2022-03-10 11:37:23.
Scientists developing gene drive mosquitoes for vector control must understand how residents of affected areas regard both the problem of mosquito-borne disease and the potential solutions offered by gene drive. This study represents an experiment in public engagement at an early stage of technology development, intended to inform lab scientists about public attitudes toward their research and inspire consideration and conversation about the social ramifications of creating mosquitoes with gene drive. Online focus groups with California residents explored views on mosquito-borne disease risk, current mosquito control methods, and the proposed development and use of different classes of gene drives to control Ae. aegypti. Rather than a dogmatic rejection of genetic engineering or gene drive, many participants expressed pragmatic concerns with cost, control, the ability to narrowly target specific species, and the challenges of mistrust and institutional cooperation. Work like this can inform the alignment of community priorities and the professional priorities of scientists and vector control specialists.
Rescue by gene swamping as a gene drive deployment strategy
20587K. D. Harris and G. Greenbaum, bioRxiv, 2022.03.08.483503. 2022-03-08 11:25:49.
Gene drives are genetic constructs that can spread deleterious alleles with potential application to population suppression of harmful species. Given that a gene drive can potentially spill over to other populations or even other species, control measures and fail-safes strategies must be considered. Gene drives are designed to generate a rapid demographic decline, while at the same time generating a dynamic change in the population’s genetics. Since these evolutionary and demographic processes are linked and are expected to occur at a similar time-scale during gene drive spread, feedback between these processes may significantly affect the outcome of deployment. To study this feedback and to understand how it affects gene drive spillovers, we developed a gene drive model that combines evolutionary and demographic dynamics in a two-population setting. The model demonstrates how feedback between evolutionary and demographic dynamics can generate additional outcomes to those generated by the evolutionary dynamics alone. We identify an outcome of particular interest, where the short-term suppression of the target population is followed by gene swamping and loss of the gene drive. This outcome could be useful for designing gene drive deployments that temporarily suppress the population, but ultimately do not remain in the population. Using our model, we demonstrate the robustness of this outcome to spillover and to the evolution of resistance, and suggest that it could be used as a fail-safe strategy for gene drive deployment.Competing Interest StatementThe authors have declared no competing interest.
Gene drives and population persistence vs elimination: The impact of spatial structure and inbreeding at low density
20529P. J. Beaghton and A. Burt, Theoretical Population Biology, 2022-03-03 08:28:52.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.
EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil
20526M. H. Collins, G. E. Potter, M. D. T. Hitchings, E. Butler, M. Wiles, J. K. Kennedy, S. B. Pinto, A. B. M. Teixeira, A. Casanovas-Massana, N. G. Rouphael, G. A. Deye, C. P. Simmons, L. A. Moreira, M. L. Nogueira, D. A. T. Cummings, A. I. Ko, M. M. Teixeir, Trials, 23:185. 2022-03-02 08:20:38.
BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.
Should we kill every mosquito on Earth?
20519J. Phelan, LiveScience, 2022-02-28 08:05:44.
Before you grab that can of bug spray, know this: While some mosquitoes are dangerous to us, not all are. Even those that are sometimes harmful tend not to feed on humans, preferring honeydew, plant sap and nectar, according to Mosquito Joe, a mosquito control company. There are around 3,500 mosquito species, but "only around 100 will potentially bite and spread disease to humans," Steven Sinkins, a professor in microbiology and tropical medicine at the Centre for Virus Research at the University of Glasgow in Scotland, told Live Science in an email. For instance, Culiseta mosquitoes often bite humans, but are not known to carry any debilitating diseases, while Toxorhynchites, which are common the world over and tend to live in forests, prefer nectar sugars to blood, according to Entomology Today. Therefore, it probably wouldn't be necessary to get rid of every mosquito species. Instead, we could target the more problematic ones, such as Aedes aegypti, which carry diseases such as yellow fever and Zika. A. aegypti is now ubiquitous, but it wasn't always this way. The species first spread out of Africa during the slave trade between the 15th and 19th centuries, through trade with Asia in the 18th and 19th centuries, and via troop movements during World War II, according to the World Mosquito Program, a nonprofit based in Australia.
A UC malaria initiative program receives grant for work researching genetically engineered mosquitoes
20483S. Slater, The California Aggie, 2022-02-23 08:39:35.
Malaria, a mosquito-borne infectious disease, was discovered in 1880, and has remained widespread in tropical regions around the equator including parts of Africa, Asia and Latin America, resulting in thousands of deaths and a significant blow to economic development in these regions. Many of the attempted strategies to eliminate malaria in the past have planned to do so by eliminating mosquitoes entirely — but according to a recent press release, the Vector Genetics Laboratory (VGL) at UC Davis, in collaboration with a UC malaria initiative program that originally started at UC Irvine, and with the financial support of a $10.2 million grant from Open Philanthropy, is taking a different approach. “Mosquitoes are a part of the ecosystem,” Greg Lanzaro, project principal investigator and director at VGL, said. “Our strategy does not eliminate mosquitoes. The mosquitoes will still be there, they’ll just be incapable of transmitting malaria. In every sense these mosquitoes are normal mosquitoes, except for the fact that they can’t transmit malaria.” The idea is called a “population modification strategy,” Lanzaro said, explaining that groups at UC Irvine and Johns Hopkins University genetically engineered mosquitoes that are incapable of transmitting the malaria parasite. “The way that malaria is transmitted is that the mosquito bites a person who has malaria and it picks up the parasite in the blood that it feeds on,” Lanzaro said. “Then the parasite develops in the mosquito so that when the mosquito bites the next person, they spread the parasite. Our mosquitoes have been engineered with a couple of genes that kill the parasite inside of the mosquito, so they’re not able to transmit.”
Regulation of genetically engineered (GE) mosquitoes as a public health tool: a public health ethics analysis
20480Z. Meghani, Globalization and Health, 18:21. 2022-02-21 08:33:18.
In recent years, genetically engineered (GE) mosquitoes have been proposed as a public health measure against the high incidence of mosquito-borne diseases among the poor in regions of the global South. While uncertainties as well as risks for humans and ecosystems are entailed by the open-release of GE mosquitoes, a powerful global health governance non-state organization is funding the development of and advocating the use of those bio-technologies as public health tools.
Considerations for homology-based DNA repair in mosquitoes: Impact of sequence heterology and donor template source
20478J. X. D. Ang, K. Nevard, R. Ireland, D.-K. Purusothaman, S. A. N. Verkuijl, L. Shackleford, E. Gonzalez, M. A. E. Anderson and L. Alphey, PLOS Genetics, 18:e1010060. 2022-02-18 08:29:29.
Author summary The field of genetic control of mosquito vectors has progressed rapidly in recent years, especially in Cas9-based control systems, due to its robustness to elicit a species-specific and dispersive control of mosquito population. To generate a Cas9-based integration, Cas9 and sgRNA are used to cleave a chromosomal locus while a plasmid DNA donor, containing a genetic cargo flanked by sequences homologous to the chromosomal locus, is supplied as a repair template. This results in the cargo being copied into the genome through HDR. This form of integration, however, is currently one of the major bottlenecks for researchers as it involves a laborious process of microinjecting mosquito embryos and has rather low integration rates. In this study, we assessed the effects of homologous sequence mismatches and various donor template forms (i.e. plasmid, ssDNA, biotinylated ds/ssDNA) on HDR. We found that sequence mismatches and non-plasmid donors reduced the efficiency and integrity of integration, respectively. By analysing the direction and length of homologous sequence that was copied into the genome concurrently with the cargo, we inferred the mechanism responsible for the integrations observed in our study. These findings will be useful to guide future construct designs for optimal HDR rates in mosquitoes.
Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development
20447A. Hoermann, T. Habtewold, P. Selvaraj, G. Del Corsano, P. Capriotti, M. G. Inghilterra, K. M. Temesgen, G. K. Christophides and N. Windbichler, bioRxiv, 2022.02.15.480588. 2022-02-17 09:41:11.
Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, Magainin 2 and Melittin. This small genetic modification, capable of efficient non-autonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites while it simultaneously reduces the lifespan of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of endemic settings.Competing Interest StatementThe authors have declared no competing interest.
An Ethical Overview of the CRISPR-Based Elimination of Anopheles gambiae to Combat Malaria
20442I. J. Wise and P. Borry, Journal of Bioethical Inquiry, 2022-02-17 09:30:10.
Approximately a quarter of a billion people around the world suffer from malaria each year. Most cases are located in sub-Saharan Africa where Anopheles gambiae mosquitoes are the principal vectors of this public health problem. With the use of CRISPR-based gene drives, the population of mosquitoes can be modified, eventually causing their extinction. First, we discuss the moral status of the organism and argue that using genetically modified mosquitoes to combat malaria should not be abandoned based on some moral value of A. gambiae. Secondly, we argue that environmental impact studies should be performed to obtain an accurate account of the possible effects of a potential eradication of the organism. However, the risks from the purposeful extinction of A. gambiae should not overtake the benefits of eradicating malaria and risk assessments should be used to determine acceptable risks. Thirdly, we argue that the eventual release of the genetically modified mosquitoes will depend on transparency, community involvement, and cooperation between different nations.
A preliminary framework for understanding the governance of novel environmental technologies: Ambiguity, indeterminateness and drift
20412F. Rabitz, M. Feist, M. Honegger, J. Horton, S. Jinnah and J. Reynolds, Earth System Governance, 12:100134. 2022-02-16 16:13:59.
We propose a conceptual framework to explain why some technologies are more difficult to govern than others in global environmental governance. We start from the observation that some technologies pose transboundary environmental risks, some provide capacities for managing such risks, and some do both. For “ambiguous” technologies, potential risks and risk management capacities are uncertain, unknown or even unknowable. Governance systems are indeterminate towards ambiguous technologies, as existing norms, rules, scripts and routines do not imply default solutions under institutional focal points. Indeterminateness can lead to institutional drift, with risks accordingly remaining unmitigated and risk management capacities remaining unexploited. We use the cases of solar geoengineering, gene drive systems and bioinformatics for illustrating this framework. As technological ambiguity may often be irresolvable, we conclude that it might force us to confront the limits to anticipatory global decision-making on matters of long-term environmental sustainability.
A Closing Window of Opportunity for Gene Drive Governance in the United States
20445K. L. Warmbrod, M. Montague and G. K. Gronvall, Health Security, 20:3-5. 2022-02-15 09:35:05.
The COVID-19 pandemic has brought forth a number of biotechnological advances to enhance the public's health: new diagnostic tests, mRNA vaccines, and new antiviral medications. Biotechnology is also being used to address global challenges like climate change, food insecurity, and building the bioeconomy, which directly or indirectly improve public health. Gene drives are one such biotechnology. They are genetically engineered systems that can alter the inheritance patterns in a host species, such as a mosquito, so that a greater percentage of its progeny inherit a specific desired trait. Research and investments in biotechnology have been used to reduce arthropod-borne infectious diseases, such as malaria and Zika, and to manage or eliminate invasive species.2 Funding thus far has been adequate. For example, Target Malaria, a global consortium of researchers developing a gene drive to decrease the burden of malaria, has an average of US$11.5 million per year in funding.3 Although no gene drive has been released into the environment yet, technologies with similar attributes have been released in field trials, notably by Oxitec in Florida
Mark-release-recapture experiment in Burkina Faso demonstrates reduced fitness and dispersal of genetically-modified sterile malaria mosquitoes
20385F. A. Yao, A.-A. Millogo, P. S. Epopa, A. North, F. Noulin, K. Dao, M. Drabo, C. Guissou, S. Kekele, M. Namountougou, R. K. Ouedraogo, L. Pare, N. Barry, R. Sanou, H. Wandaogo, R. K. Dabire, A. McKemey, F. Tripet and A. Diabaté, Nature Communications, 13:796. 2022-02-10 09:11:33.
Every year, malaria kills approximately 405,000 people in Sub-Saharan Africa, most of them children under the age of five years. In many countries, progress in malaria control has been threatened by the rapid spread of resistance to antimalarial drugs and insecticides. Novel genetic mosquito control approaches could play an important role in future integrated malaria control strategies. In July 2019, the Target Malaria consortium proceeded with the first release of hemizygous genetically-modified (GM) sterile and non-transgenic sibling males of the malaria mosquito Anopheles coluzzii in Burkina Faso. This study aimed to determine the potential fitness cost associated to the transgene and gather important information related to the dynamic of transgene-carrying mosquitoes, crucial for next development steps. Bayesian estimations confirmed that GM males had lower survival and were less mobile than their wild type (WT) siblings. The estimated male population size in Bana village, at the time of the release was 28,000 - 37,000. These results provide unique information about the fitness and behaviour of released GM males that will inform future releases of more effective strains of the A. gambiae complex.
The spore killers, fungal meiotic driver elements
20390A. A. Vogan, I. Martinossi-Allibert, S. L. Ament-Velásquez, J. Svedberg and H. Johannesson, Mycologia, 2022-02-09 09:22:39.
During meiosis, both alleles of any given gene should have equal chances of being inherited by the progeny. There are a number of reasons why, however, this is not the case, with one of the most intriguing instances presenting itself as the phenomenon of meiotic drive. Genes that are capable of driving can manipulate the ratio of alleles among viable meiotic products so that they are inherited in more than half of them. In many cases, this effect is achieved by direct antagonistic interactions, where the driving allele inhibits or otherwise eliminates the alternative allele. In ascomycete fungi, meiotic products are packaged directly into ascospores; thus, the effect of meiotic drive has been given the nefarious moniker, "spore killing." In recent years, many of the known spore killers have been elevated from mysterious phenotypes to well-described systems at genetic, genomic, and molecular levels. In this review, we describe the known diversity of spore killers and synthesize the varied pieces of data from each system into broader trends regarding genome architecture, mechanisms of resistance, the role of transposable elements, their effect on population dynamics, speciation and gene flow, and finally how they may be developed as synthetic drivers. We propose that spore killing is common, but that it is under-observed because of a lack of studies on natural populations. We encourage researchers to seek new spore killers to build on the knowledge that these remarkable genetic elements can teach us about meiotic drive, genomic conflict, and evolution more broadly.
Gene-drive mosquitoes, a prospect for future malaria control
21770S. A. Monawwer, A. O. I. Alzubaidi, F. Yasmin, S. M. Q. Haimour, S. M. I. Shay and I. Ullah, Pan African Medical Journal, 41:2-6. 2022-02-08 07:58:25.
Despite major developments in malaria control over the past two decades, the disease continues to scourge the human population across the globe. Rising concerns such as insecticide resistance amongst vector mosquitoes are a cause of huge fear amongst healthcare providers and policymakers. Amidst such dire circumstances, a recent development may form the blueprint for future malaria control as for the first time ever researchers were able to decimate an entire mosquito population using gene-drive technology within a span of one year in a multi-generation, ecologically challenging study. Despite some concerns, the technology displayed a high potential of becoming a powerful tool in malaria control.
Articulating ethical principles guiding Target Malaria’s engagement strategy
20320A. J. Roberts and D. Thizy, Malaria Journal, 21:35. 2022-02-05 09:13:03.
Progress in gene drive research has engendered a lively discussion about community engagement and the ethical standards the work hinges on. While there is broad agreement regarding ethical principles and established best practices for conducting clinical public health research, projects developing area-wide vector control technologies and initiating ambitious engagement strategies raise specific questions: who to engage, when to engage, and how? When responding to these fundamental questions, with few best practices available for guidance, projects need to reflect on and articulate the ethical principles that motivate and justify their approach. Target Malaria is a not-for-profit research consortium that aims to develop and share malaria control and elimination technology. The consortium is currently investigating the potential of a genetic technique called gene drive to control populations of malaria vectoring mosquito species Anopheles gambiae. Due to the potentially broad geographical, environmental impact of gene drive technology, Target Malaria has committed to a robust form of tailored engagement with the local communities in Burkina Faso, Mali, and Uganda, where research activities are currently taking place. This paper presents the principles guiding Target Malaria’s engagement strategy. Herein the authors (i) articulate the principles; (ii) explain the rationale for selecting them; (iii) share early lessons about the application of the principles. Since gene drive technology is an emerging technology, with few best practices available for guidance, the authors hope by sharing these lessons, to add to the growing literature regarding engagement strategies and practices for area-wide vector control, and more specifically, for gene drive research.
Could Crispr Flip the Switch on Insects’ Resistance to Pesticides?
20288E. Mullin, WIRED, 2022-02-02 11:53:17.
WHILE THE COVID-19 pandemic raged across the world in 2020, another disease was quietly infecting more than 220 million people on the continent of Africa: malaria. That year, the disease led to more than 600,000 deaths, most of them children. Caused by the parasite Plasmodium, the illness is spread through the bites of infected female Anopheles mosquitoes. Insecticide-treated bed nets and indoor spraying have long been some of the most effective strategies for combating the disease. But decades of using these chemicals has lessened their potency. It happens like this: Insecticides kill off most of the mosquitoes in an area. But a small number may survive because something about their genetic makeup makes them unaffected by the pesticide. Mosquitoes within that small population mate with each other and pass on their genes to their offspring, breeding more resistant mosquitoes. In some cases, resistance has built up just a few years after the introduction of an insecticide. It makes fighting deadly mosquitoes a constant game of whack-a-mole. Insecticides remain the frontline in fighting malaria, because interventions like building mosquito-resistant housing are still experimental, and the effort to develop a vaccine has taken decades. Last summer the World Health Organization recommended Mosquirix, the first anti-parasitic vaccine, for African children under age 5, but it is only 30 percent effective at preventing serious disease, and will take many years to achieve approval and distribution among individual nations.
Gene Editing Is Popular, But Controversial, Research Are
20387Relias, RELIAS MEDIA, 2022-02-01 09:18:26.
Gene drive research carries great potential for controlling insect vectors of devastating diseases, but there are multiple unresolved ethical concerns. Unanticipated “downstream” effects on ecosystems, or in organisms that carry the gene drive machinery, are possible. To help researchers balance risks and benefits for society and humanity, scientists involved in the Controlling and Countering Gene Editing in Mosquitoes research project developed a code of ethics for gene drive research. Today, gene drive researchers are focused on diseases that mosquitoes carry. The goal is to make a mosquito that cannot infect a person with malaria. “All of a sudden, it’s become a very hot research area. With the discovery of CRISPR, everybody wants to apply CRISPR to everything. But here is an area where it actually makes sense,” says lead author George J. Annas, JD, MPH, director of the Center for Health Law, Ethics, and Human Rights at Boston University.
Crisp Genes
20283J. Mckenna, The Simple Science, 2022-01-29 11:44:36.
Imagine we had the power to use genetic technologies to stop one of humanity’s most dangerous predators. What is that predator? Sharks? Crocodiles? Snakes? Think far, far smaller. It is in fact, the mosquito.Mosquitos cause all sorts of nasty diseases like the Zika Virus, Dengue Fever, Yellow Fever, and malaria. While nobody really wants to contract any of those diseases, and they’ll all make you pretty miserable, they’re nothing compared to the frankly hellacious malaria being one of the single biggest killers of humans in history. Well, plot twist, we actually do have the technology and it comes in the form of some genetic machinery discovered in bacteria: CRISPR-Cas9 (or CRISPR for short).
Scientists find transmission chain-breaker, give new hope for fight against malaria
20473ANI, ANI, 2022-01-27 08:09:19.
A recent study, published online in 'PLoS Biology', has revealed that blocking a key protein found in Anopheles gambiae mosquitoes -- the principal vector for malaria transmission to humans in Africa could thwart infection with malaria parasites and thus prevent them from transmitting the parasites to humans. The study was undertaken by Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health. In a lab experiment, the researchers used CRISPR/Cas9 gene-editing technology to delete the gene for a protein called CTL4 from Anopheles gambiae mosquitoes. This deletion made the mosquitoes highly resistant to the malaria parasite. The researchers found that disrupting the CTL4 protein brought a 64 percent decrease in infection prevalence. The researchers believe that targeting the CTL4 protein could be the basis for new strategies to control malaria in regions where it is still endemic.
Gene Drives in the U.K., U.S., and Australian Press (2015–2019): How a New Focus on Responsibility Is Shaping Science Communication
20217A. Stelmach, B. Nerlich and S. Hartley, Science Communication, 10755470211072245. 2022-01-25 16:28:49.
Gene drive is a controversial biotechnology for pest control. Despite a commitment from gene drive researchers to responsibility and the key role of the media in debates about science and technology, little research has been conducted on media reporting of gene drive. We employ metaphor and discourse analysis to explore how responsibility is reflected in the coverage of this technology in the U.S., U.K., and Australian press. The findings reveal a rhetorical strategy of trust-building by evoking the moral attributes of gene drive researchers. We discuss the implications of these findings for the communication of new technologies.
Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species
20177G. Rašić, N. F. Lobo, E. H. Jeffrey Gutiérrez, C. H. Sánchez and J. M. Marshall, Frontiers in Genetics, 12:780327. 2022-01-25 09:18:49.
As gene drive mosquito projects advance from contained laboratory testing to semi-field testing and small-scale field trials, there is a need to assess monitoring requirements to: i) assist with the effective introduction of the gene drive system at field sites, and ii) detect unintended spread of gene drive mosquitoes beyond trial sites, or resistance mechanisms and non-functional effector genes that spread within trial and intervention sites. This is of particular importance for non-localized gene drive projects, as the potential scale of intervention means that monitoring is expected to be more costly than research, development and deployment. Regarding monitoring needs for population replacement systems, lessons may be learned from experiences with Wolbachia-infected mosquitoes, and for population suppression systems, from experiences with releases of genetically sterile male mosquitoes. For population suppression systems, assessing monitoring requirements for tracking population size and detecting rare resistant alleles are priorities, while for population replacement systems, allele frequencies must be tracked, and pressing concerns include detection of gene drive alleles with non-functional effector genes, and resistance of pathogens to functional effector genes. For spread to unintended areas, open questions relate to the optimal density and placement of traps and frequency of sampling in order to detect gene drive alleles, drive-resistant alleles or non-functional effector genes while they can still be effectively managed. Invasive species management programs face similar questions, and lessons may be learned from these experiences. We explore these monitoring needs for gene drive mosquito projects progressing through the phases of pre-release, release and post-release.
A gene drive does not spread easily in populations of the honey bee parasite Varroa destructor
20173N. R. Faber, A. B. Meiborg, G. R. McFarlane, G. Gorjanc and B. A. Harpur, Apidologie, 52:1112-1127. 2022-01-25 09:13:37.
Varroa mites (Varroa destructor) are the most significant threat to beekeeping worldwide. They are directly or indirectly responsible for millions of colony losses each year. Beekeepers are somewhat able to control varroa populations through the use of physical and chemical treatments. However, these methods range in effectiveness, can harm honey bees, can be physically demanding on the beekeeper, and do not always provide complete protection from varroa. More importantly, in some populations varroa mites have developed resistance to available acaricides. Overcoming the varroa mite problem will require novel and targeted treatment options. Here, we explore the potential of gene drive technology to control varroa. We show that spreading a neutral gene drive in varroa is possible but requires specific colony-level management practices to overcome the challenges of both inbreeding and haplodiploidy. Furthermore, continued treatment with acaricides is necessary to give a gene drive time to fix in the varroa population. Unfortunately, a gene drive that impacts female or male fertility does not spread in varroa. Therefore, we suggest that the most promising way forward is to use a gene drive which carries a toxin precursor or removes acaricide resistance alleles. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13592-021-00891-5.
Gene drives for vertebrate pest control: realistic spatial modelling of eradication probabilities and times for island mouse populations
20171A. Birand, P. Cassey, J. V. Ross, J. C. Russell, P. Thomas and T. A. A. Prowse, Molecular Ecology, 2022-01-24 09:06:03.
Abstract Invasive alien species continue to threaten global biodiversity. CRISPR-based gene drives, which can theoretically spread through populations despite imparting a fitness cost, could be used to suppress or eradicate pest populations. We develop an individual-based, spatially explicit, stochastic model to simulate the ability of CRISPR-based homing and X-chromosome shredding drives to eradicate populations of invasive house mice (Mus muculus) from islands. Using the model, we explore the interactive effect of the efficiency of the drive constructs and the spatial ecology of the target population on the outcome of a gene-drive release. We also consider the impact of polyandrous mating and sperm competition, which could compromise the efficacy of some gene-drive strategies. Our results show that both drive strategies could be used to eradicate large populations of mice. Whereas parameters related to drive efficiency and demography strongly influence drive performance, we find that sperm competition following polyandrous mating is unlikely to impact the outcome of an eradication effort substantially. Assumptions regarding the spatial ecology of mice influenced the probability of and time required for eradication, with short-range dispersal capacities and limited mate-search areas producing `chase' dynamics across the island characterised by cycles of local extinction and recolonization by mice. We also show that highly efficient drives are not always optimal, when dispersal and mate-search capabilities are low. Rapid local population suppression around the introduction sites can cause loss of the gene drive before it can spread to the entire island. We conclude that, although the design of efficient gene drives is undoubtedly critical, accurate data on the spatial ecology of target species is critical for predicting the result of a gene-drive release.
Could we delete diseases passed down through our DNA?
20278E. Rayne, SYFY, 2022-01-23 11:33:23.
What has now been proven possible was once the stuff of science fiction dreams. CRISPR has shown it can successfully edit out detrimental genetic conditions before they are inherited — which could mean the beginning of the end for hereditary diseases. It could also help obliterate invasive species from ecosystems under attack. Imagine if gene editing could delete conditions you never asked to be born with while getting rid of the cane toad invasion in Australia. CRISPR-Cas9 has been able to successfully edit DNA again and again, but it’s never done anything like this. Kind of like DNA autocorrecting itself, the editing needs to make deletion in a cell happen during a certain phase of meiosis. Researcher Kimberly Cooper of UC San Diego, who coauthored a study recently published in PLOS Biology, figured out exactly when to get to that meiotic window and how to control which copies of genes are handed down to the next generation.
Ethical Considerations for Gene Drive: Challenges of Balancing Inclusion, Power and Perspectives
20139A. Kormos, G. C. Lanzaro, E. Bier, V. Santos, L. Nazare, J. Pinto, A. A. dos Santos and A. James, Frontiers in Bioengineering and Biotechnology, 2022-01-21 13:24:13.
Progress in gene-drive research has stimulated discussion and debate on ethical issues including community engagement and consent, policy and governance, and decision-making involved in development and deployment. Many organizations, academic institutions, foundations, and individual professionals have contributed to ensuring that these issues are considered prior to the application of gene-drive technology. Central topics include co-development of the technology with local stakeholders and communities and reducing asymmetry between developers and end-users. Important questions include with whom to conduct engagement and how to define community acceptance, develop capacity-building activities, and regulate this technology. Experts, academics, and funders have suggested that global frameworks, standards, and guidelines be developed to direct research in answering these important questions. Additionally, it has been suggested that ethical principles or commitments be established to further guide research practices. The challenging and interesting contradiction that we explore here is that the vast majority of these conversations transpire with little or no input from potential end-users or stakeholders who, we contend, should ultimately determine the fate of the technology in their communities. The question arises, whose concerns regarding marginalization, disempowerment, and inequity should be included in discussions and decisions concerning how inequities are perceived and how they may be addressed? At what stage will true co-development occur and how will opinions, perspectives and knowledge held by low-income country stakeholders be applied in determining answers to the questions regarding the ethics being debated on the academic stage? Our opinion is that the time is now.
Gene drives and metaphors
20127B. Nerlich, Making Science Public, 2022-01-21 09:32:53.
I have been writing about developments in the biosciences for twenty years. In that time, I have covered a wide variety of topics, such as cloning, genomics, the human genome project, the microbiome project, faecal microbial transplants, synthetic biology, epigenetics, genome editing and now gene drive. I was lucky enough to get many reflections on these topics (by me and other colleagues!) published in the appropriately titled journal New Genetics and Society. The newest addition to this family of articles is one on gene drives – a range of controversial technologies that can potentially be used for the eradication or conservation of animal species – written with Aleksandra Stelmach. It has a certain family resemblance with the other articles, as it too deals with the use of metaphor in framing a particular issue in the biosciences. However, it is also quite different. While the other articles mainly examined media articles on the genetic or genomic topics they covered, this article is based on the analysis of interviews with gene drive experts and practitioners reflecting on their and others’ uses of metaphors. The article was prompted by emerging findings from a Wellcome Trust funded project, led by Sarah Hartley, aiming to increase understanding of how people communicate about gene drives. Aleksandra carried out 30 interviews with scientists, experts, and NGOs working in sectors or being involved in sectors relating to gene drive research in the United Kingdom, the United States, and Australia.
CRISPR Technology Can Eliminate Disease-Spreading Mosquitoes
20133S. Krishana, Now, 2022-01-19 13:10:41.
Scientists have uncovered a new technique they call the “precision-guided sterile insect technique,” or pgSIT. While most CRISPR procedures affect organisms that spread diseases by passing a gene change down generations, this system is more limited. It targets male mosquito genes that are linked to fertility. As a result of changing these genes, any offspring these mosquitoes have would be infertile. “pgSIT is a new scalable genetic control system that uses a CRISPR-based approach to engineer deployable mosquitoes that can suppress populations,” said Omar Akbari, one of the study’s authors. “Males don’t transmit diseases, so the idea is that, as you release more and more sterile males, you can suppress the population without relying on harmful chemicals and insecticides.” But it’s the female population that spreads diseases, so pgSIT targets them, as well. According to the study, the CRISPR technology treatment renders female mosquitoes unable to fly or hold their wings up. It also makes them slower and more lethargic in their movements. Combined, these effects lower the chances that these female mosquitoes will mate or successfully find a blood source and attach to it to spread disease.
Genetic Strategy Reverses Insecticide Resistance
20108H. Tasoff, The Current, 2022-01-18 17:08:09.
University of California biologists have now developed a method that reverses insecticide resistance using CRISPR/Cas9 technology. A team including UC Santa Barbara researchers Craig Montell(link is external) and Menglin Li(link is external), UC San Diego researchers Bhagyashree Kaduskar, Raja Kushwah and Professor Ethan Bier of UCSD’s Tata Institute for Genetics and Society (TIGS) used the genetic editing tool to replace an insecticide-resistant gene in fruit flies with the normal insecticide-susceptible form. Their achievement, described in Nature Communications(link is external), could significantly reduce the amount of insecticides used. “This strategy could be used to reverse the resistance of mosquito disease vectors that spread devastating diseases that impact hundreds of millions of people each year,” said Craig Montell, a professor of molecular, cellular and developmental Biology at UC Santa Barbara.
Analysis of a Cas12a-based gene-drive system in budding yeast
20029I. C. Lewis, Y. Yan and G. C. Finnigan, Access Microbiol, 3:000301. 2022-01-14 09:19:55.
The discovery and adaptation of CRISPR/Cas systems within molecular biology has provided advances across biological research, agriculture and human health. Genomic manipulation through use of a CRISPR nuclease and programmed guide RNAs has become a common and widely accessible practice. The identification and introduction of new engineered variants and orthologues of Cas9 as well as alternative CRISPR systems such as the type V group have provided additional molecular options for editing. These include distinct PAM requirements, staggered DNA double-strand break formation, and the ability to multiplex guide RNAs from a single expression construct. Use of CRISPR/Cas has allowed for the construction and testing of a powerful genetic architecture known as a gene drive within eukaryotic model systems. Our previous work developed a drive within budding yeast using Streptococcus pyogenes Cas9. Here, we installed the type V Francisella novicida Cas12a (Cpf1) nuclease gene and its corresponding guide RNA to power a highly efficient artificial gene drive in diploid yeast. We examined the consequence of altering guide length or introduction of individual mutational substitutions to the crRNA sequence. Cas12a-dependent gene-drive function required a guide RNA of at least 18 bp and could not tolerate most changes within the 5' end of the crRNA.
Gene drive communication: exploring experts’ lived experience of metaphor use
20032B. Nerlich and A. Stelmach, New Genetics and Society, 2022-01-13 09:20:04.
Metaphors have been crucial in making genetics and genomics public, fromthe code and the book of life to genetic scissors and gene surgery. A newfield is emerging called“gene drive”–a range of controversial technologiesthat can potentially be used for the eradication or conservation of animalspecies. At the same time, metaphors are emerging to talk about thepromises and dangers of“gene drive”. In this article we use thematicanalysis to examine thirty interviews with gene drive science andcommunication experts, and stakeholders, focusing on how they talk abouttheir lived experience of metaphor use in the context of gene drivecommunication, including their struggle to remember salient metaphors andtheir reflections on which metaphors to use and which to avoid. We discussthe significance of ourfindings for research and practice of responsiblescience communication.
Scientists expand CRISPR-Cas9 genetic inheritance control in mammals
20038M. Aguilera, Phys Org, 2022-01-12 09:43:07.
Led by graduate student Alexander Weitzel, Grunwald, Cooper and their colleagues have now succeeded in developing CRISPR-Cas9 inheritance control in male mice by shifting the gene editing window to more closely match the timing of meiosis in both sexes. Their results were published December 23, 2021 in the journal PLOS Biology. The achievement advances the prospects of scientists being able to use genetic editing for new laboratory models in an array of research pursuits, from investigations of human disease to therapeutic drug design to invasive species removal. "For these gene conversion strategies to work in any context—in the lab or in wild populations—you need the mechanism of gene conversion to work in both males and females," said Cooper, associate professor in the Section of Cell and Developmental Biology, Division of Biological Sciences. "It seems as though the reason this process was previously working in females is because we were closer to the female meiotic window. Now that we've moved Cas9 expression to within the meiotic window in males, it works in them too."
Insect Allies – Assessment of a Viral Approach to Plant Genome Editing
20036K. Pfeifer, J. L. Frieß and B. Giese, Integrated Environmental Assessment and Management, 2022-01-12 09:38:06.
The DARPA program Insect Allies has already sparked scientific debate concerning technology assessment-related issues, among which the most prevalent is that of dual use potential. As apart from the issues concerning peaceful applications, the technology also provides the blueprint for a potential bioweapon as further evidenced by a recent publication. However, the combination of a virus-induced genetic modification of crop plants in the field using genetically modified insect vectors poses an increased risk potential in comparison to the hitherto existing use of genetically modified organisms. The technology's high depth of intervention enables a number of sources for hazard and a by trend high exposure, but it is also encumbered with notable deficits in knowledge. These issues call for a thorough technology assessment. This article aims to provide an initial characterization from a technology assessment perspective, focusing on potential sources of risk for this novel invasive environmental biotechnology at an early stage of research and development. This article is protected by copyright. All rights reserved.© 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Reversing insecticide resistance with allelic-drive in Drosophila melanogaster
20085B. Kaduskar, R. B. S. Kushwah, A. Auradkar, A. Guichard, M. Li, J. B. Bennett, A. H. F. Julio, J. M. Marshall, C. Montell and E. Bier, Nature Communications, 13:291. 2022-01-12 09:16:33.
A recurring target-site mutation identified in various pests and disease vectors alters the voltage gated sodium channel (vgsc) gene (often referred to as knockdown resistance or kdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity of kdr mutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate common kdr mutations in isogenic laboratory Drosophila strains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two different kdr mutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistant kdr mutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles.
The prince, the mayor, and the U.S. fish that ate Japan
20103C. Elliot, National Geographic, 2022-01-11 16:44:32.
When Crown Prince Akihito visited Chicago on October 3, 1960, his sole request was to visit Shedd Aquarium. Then Mayor Richard J. Daley, an avid angler, presented the prince with a gift that he scooped with a net from one of the tanks himself: 18 bluegills, the official Illinois state fish. The 26-year-old future emperor was already a passionate ichthyologist, and he planned to stock the exotic fish in the moat surrounding his palace, according to accounts in the Chicago Tribune at the time. At windy Chicago O’Hare International Airport the next day with Princess Michiko, Akihito bid the city farewell, carrying a gift that he couldn’t have imagined would cause a decades-long ecological crisis in his homeland. In the intervening six decades, the bluegills became an invasive, species-destroying nightmare, crowding Japanese freshwater lakes and rivers and destroying native fish biodiversity, says Kenji Saitoh, a researcher at the country’s Fisheries Resources and Education Agency. Fortunately, science has marched on in 60 years. Now, Japanese geneticists are experimenting with the gene editing wizardry of CRISPR to sterilize the invasive bluegills. If the initiative succeeds, wildlife managers could use the same technique to rid the U.S. of damaging aquatic invasives such as the Asian carp.
iGEM and Gene Drives: A Case Study for Governance
20040P. Millett, T. Alexanian, M. J. Palmer, S. W. Evans, T. Kuiken and K. Oye, Health Security, 2022-01-11 09:49:06.
Gene drives have already challenged governance systems. In this case study, we explore the International Genetically Engineered Machine (iGEM) competition's experiences in gene drive-related research and lessons in developing, revising, and implementing a governance system. iGEM's experiences and lessons are distilled into 6 key insights for future gene drive policy development in the United States: (1) gene drives deserve special attention because of their potential for widescale impact and remaining uncertainty about how to evaluate intergenerational and transboundary risks; (2) an adaptive risk management approach is logical for gene drives because of the rapidly changing technical environment; (3) review by individual technical experts is limited and may fail to incorporate other forms of expertise and, therefore, must be complemented with a range of alternative governance methods; (4) current laboratory biosafety and biosecurity review processes may not capture gene drive research or its components in practice even if they are covered theoretically; (5) risk management for research and development must incorporate discussions of values and broader implications of the work; and (6) a regular technology horizon scanning capacity is needed for the early identification of advances that could pose governance system challenges.
The Need for a Tiered Registry for US Gene Drive Governance
20003K. L. Warmbrod, A. L. Kobokovich, R. West, G. K. Gronvall and M. Montague, Health Security, 2022-01-10 10:08:26.
A great deal of attention has been focused on the potential risks of gene drives, the kinds of biosafety protections they may require, and how they may be reversed; however, less attention has been paid to the systems that would be useful to have in place in the future, when multiple gene drives may be fielded in multiple species, environments, and countries.4-7 The need for coordinated governance of these technologies will become more pressing as gene drive technologies advance and more drives are created to address other vector-borne diseases like the West Nile virus, agricultural pest management, or invasive species. Gene drives carry different inherent risks compared with other genetically modified organisms (GMOs). Existing governance mechanisms for traditional GMOs are insufficient for oversight of gene drives, which require different systems to assess their usefulness and safety. To address the needs for enhanced oversight, we propose a tiered registry system, similar to the clinical trials databases, which can provide government officials, researchers, biotechnology companies, and the public with useful information about ongoing gene drive research or previously released gene drives. Such a resource would enable scientists to confirm that new gene drives would not interfere with existing drives, provide the public with the information needed to make informed decisions concerning consent for release of gene drives, provide researchers with technical information needed to prevent collisions of independent projects modifying the same organism, and provide regulators with information critical for effective oversight. We propose that the US government should implement such a registry for gene drives in the United States, which does not have a robust gene drive regulatory system in place and is not party to the international treaty most relevant for international gene drive regulation, the Convention on Biological Diversity.8 In this commentary, we describe current efforts to safely regulate gene drive and similar genetic technologies worldwide and how the United States could build a tiered registry database that is specifically designed to regulate such technologies throughout a drive's life cycle.
An Introduction to Containment Recommendations for Gene Drive Mosquitoes and the Laboratory Rearing of Genetically Engineered Mosquitoes in Africa
20044S. Higgs, Vector-Borne and Zoonotic Diseases, 2022-01-06 10:04:57.
The prospect of using genetically engineered arthropods to reduce the incidence of vector-borne diseases either indirectly by suppressing vector populations or directly by replacing wild-type vector species with less competent ones has long been discussed; however, only in the past few years has this become feasible. The advent of CRISPR/Cas9-based gene drive and its application to mosquitoes have been a critical factor in bringing the dream to reality, but with opportunity also comes responsibility. Safe and secure handling of genetically engineered arthropods under laboratory/insectary conditions was considered in the original and revised ACGs, and under field conditions by Benedict et al. (2008). Although not discussed in these ACGs, hence the need for this addendum, Benedict et al. (2018) discussed containment and management of gene drive arthropods as distinct from genetically modified mosquitoes under laboratory conditions. A prerequisite for the application of engineered mosquitoes for mosquito-borne disease control is the rearing of these mosquitoes in countries where releases will ultimately occur. In 2018, three companion articles were published in VBZ that discussed this very issue (Mumford et al. 2018, Quinlan et al. 2018a, 2018b), with James et al. (2020) discussing efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing. In this issue of VBZ, we publish two highly relevant articles that coincidentally, although submitted independently, are complementary.
Preparing an Insectary in Burkina Faso to Support Research in Genetic Technologies for Malaria Control
20042C. Guissou, M. M. Quinlan, R. Sanou, R. K. Ouédraogo, M. Namountougou and A. Diabaté, Vector-Borne and Zoonotic Diseases, 2022-01-06 09:53:59.
The Institut de Recherche en Sciences de la Santé (IRSS) of Burkina Faso, West Africa, was the first African institution to import transgenic mosquitoes for research purposes. A shift from the culture of mosquito research to regulated biotechnology research and considerable management capacity is needed to set up and run the first insectary for transgenic insects in a country that applied and adapted the existing biosafety framework, first developed for genetically modified (GM) crops, to this new area of research. The additional demands arise from the separate regulatory framework for biotechnology, referencing the Cartagena Protocol on Biosafety, and the novelty of the research strain, making public understanding and acceptance early in the research pathway important. The IRSS team carried out extensive preparations following recommendations for containment of GM arthropods and invested efforts in local community engagement and training with scientific colleagues throughout the region. Record keeping beyond routine practice was established to maintain evidence related to regulatory requirements and risk assumptions. The National Biosafety Agency of Burkina Faso, Agence Nationale de Biosécurité (ANB), granted the permits for import of the self-limiting transgenic mosquito strain, which took place in November 2016, and for conducting studies in the IRSS facility in Bobo-Dioulasso. Compliance with permit terms and conditions of the permits and study protocols continued until the conclusion of studies, when the transgenic colonies were terminated. All this required close coordination between management and the insectary teams, as well as others. This article outlines the experiences of the IRSS to support others undertaking such studies. The IRSS is contributing to the ongoing development of genetic technologies for malaria control, as a partner of Target Malaria (https://targetmalaria.org). The ultimate objective of the innovation is to reduce malaria transmission by using GM mosquitoes of the same species released to reduce the disease-vectoring native populations of Anopheles gambiae s.l.
Stakeholder engagement to inform the risk assessment and governance of gene drive technology to manage spotted-wing drosophila
20212A. E. Kokotovich, S. K. Barnhill-Dilling, J. E. Elsensohn, R. Li, J. A. Delborne and H. Burrack, Journal of Environmental Management, 307:114480. 2022-01-04 15:32:08.
Emerging biotechnologies, such as gene drive technology, are increasingly being proposed to manage a variety of pests and invasive species. As one method of genetic biocontrol, gene drive technology is currently being developed to manage the invasive agricultural pest spotted-wing drosophila (Drosophila suzukii, SWD). While there have been calls for stakeholder engagement on gene drive technology, there has been a lack of empirical work, especially concerning stakeholder engagement to inform risk assessment. To help address this gap and inform future risk assessments and governance decisions for SWD gene drive technology, we conducted a survey of 184 SWD stakeholders to explore how they define and prioritize potential benefits and potential adverse effects from proposed SWD gene drive technology. We found that stakeholders considered the most important potential benefits of SWD gene drive technology to be: 1) Decrease in the quantity or toxicity of pesticides used, and 2) Decrease in SWD populations. Stakeholders were most concerned about the potential adverse effects of: 1) Decrease in beneficial insects, 2) Increase in non-SWD secondary pest infestations, and 3) Decrease in grower profits. Notably, we found that even stakeholders who expressed support for the use of SWD gene drive technology expressed concerns about potential adverse effects from the technology, emphasizing the need to move past simplistic, dichotomous views of what it means to support or oppose a technology. These findings suggest that instead of focusing on the binary question of whether stakeholders support or oppose SWD gene drive technology, it is more important to identify and assess the factors that are consequential to stakeholder decision making – including, for example, exploring whether and under what conditions key potential adverse effects and potential benefits would result from the use of SWD gene drive technology.
Information Sharing in Senegal on the Gene Drive Technology as a potential Complementary Tool for Malaria Vector Control
19902AUDA-NEPAD, AUDA-NEPAD, 2022-01-04 08:23:49.
AUDA-NEPAD in partnership with the National Biosafety Authority (Autorité Nationale de Biosécurité (ANB) in Senegal organized an Information sharing meeting on the gene drive technology as a complementary tool for malaria vector control, from 22-23 December 2021, in Somone, Senegal. The key objective of the meeting was to discuss the opportunities offered by gene drive technology for malaria control, based on the current state of art of knowledge and experiences from countries that are testing this approach. Sixty people, including key stakeholders from relevant institutions in Senegal and experts from Burkina Faso and Mali took part in the meeting. In his opening remarks, Mr. Ousseynou Kassé, Executive Director of ANB thanked AUDA-NEPAD for the support provided in the organization of this meeting. He also thanked the experts from Burkina Faso and Mali who came to share their experiences on the subject. “We started the discussions on the Gene Drive approach some years ago at the COP-MOP meeting held in Mexico and we continued it in the past years in the sub-region. Recently we were in Accra twice to discuss the same topic ahead of the next COP-MOP meeting”, he said. Mr. Yero Dé, Chairperson of the Orientation Council of ANB, highlighted that the meeting seeks to improve stakeholders’ understanding of the gene drive technology as a novel malaria control approach. “We need to consider adopting this new approach through an open discussion on how this technology could be used in the health sector and in particular in malaria control and elimination. Malaria mortality rate is very high in most of our countries and the efforts deployed so far to control the disease face important challenges, including the resistance of the vector to the current treatments”, he further stated.
Intervention of Modern Genetic Tools for Managing Insect Pests of Fruit Crops
25476G. S. Miglani, S. Singh, Z. Li and R. K. Sandhu, Genetic Methods and Tools for Managing Crop Pests, 2022-01-01 09:00:36.
Merits and demerits of select modern genetic tools as sterile insect technique, repressible dominant lethal, engineering insect pests, transgenic crops, primary resistance management, gene silencing RNA interference, genome-editing-based methods, autocidal insect control techniques, and genomics approaches for pest management have been discussed. Application of these methods to manage insect pests of fruit crops have been dealt with. Finally, new vision to pest control and future prospects in the utilization of molecular genetics-based tools for insect pest management has been presented.
Stakeholder Views on Engagement, Trust, Performance, and Risk Considerations About Use of Gene Drive Technology in Agricultural Pest Management
19900C. L. Goldsmith, K. E. Kang, E. Heitman, Z. N. Adelman, L. W. Buchman, D. Kerns, X. Liu, R. F. Medina and A. Vedlitz, Health Security, 2021-12-31 08:17:50.
Gene drive is an experimental technique that may make it possible to alter the genetic traits of whole populations of a species through the genetic modification of a relatively small number of individuals. This technology is sufficiently new that literature on the understanding and views of stakeholders and the public regarding the use of gene drive organisms in agricultural pest management is just beginning to emerge. Our team conducted a 2-pronged engagement process with Texas gene drive agricultural stakeholders to ascertain their values, beliefs, and preferences about the efficacy, safety, and risk management considerations of gene drive technology as a potential tool for agricultural pest management. We found that a majority of stakeholders support gene drive research and its potential use for managing agricultural pests. Our work with stakeholders confirms both their willingness to be engaged and the importance they place on stakeholder and public engagement regarding these issues, as well as the need to address these issues before use of gene drive as a pest management mechanism will be accepted and trusted.
Facilitating the Conversation: Gene Drive Classification
19766J. Overcash and A. Golnar, Health Security, 2021-12-29 13:09:10.
Gene drives are an emerging technology with tremendous potential to impact public health, agriculture, and conservation. While gene drives can be described simply as selfish genetic elements (natural or engineered) that are inherited at non-Mendelian rates, upon closer inspection, engineered gene drive technology is a complex class of biotechnology that uses a diverse number of genetic features to bias rates of inheritance. As a complex technology, gene drives can be difficult to comprehend, not only for the public and stakeholders, but also to risk assessors, risk managers, and decisionmakers not familiar with gene drive literature. To address this difficulty, we describe a gene drive classification system based on 5 functional characteristics. These characteristics include a gene drive's objective, mechanism, release threshold, range, and persistence. The aggregate of the gene drive's characteristics can be described as the gene drive's architecture. Establishing a classification system to define different gene drive technologies should make them more comprehensible to the public and provide a framework to guide regulatory evaluation and decisionmaking.
Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework
19764S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer, PLoS Comput Biol, 17:e1009660. 2021-12-29 13:01:20.
Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among invaders that induce population collapse, and could be deployed even where traditional control methods are impractical or prohibitively expensive. Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit, allows for overlapping generations and a fluctuating population size, and includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters. The computational burden of evaluating a model with such a high number of parameters presents a substantial barrier to a comprehensive understanding of its outcome space. We therefore accompany our population model with a meta-model that utilizes supervised machine learning to approximate the outcome space of the underlying model with a high degree of accuracy. This enables us to conduct an exhaustive inquiry of the population model, including variance-based sensitivity analyses using tens of millions of evaluations. Our results suggest that sufficiently capable gene drive systems have the potential to eliminate island populations of rodents under a wide range of demographic assumptions, though only if resistance can be kept to a minimal level. This study highlights the power of supervised machine learning to identify the key parameters and processes that determine the population dynamics of a complex evolutionary system.
Meiotic Cas9 expression mediates gene conversion in the male and female mouse germline
19726A. J. Weitzel, H. A. Grunwald, C. Weber, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper, PLOS Biology, 19:e3001478. 2021-12-23 12:46:23.
Highly efficient gene conversion systems have the potential to facilitate the study of complex genetic traits using laboratory mice and, if implemented as a “gene drive,” to limit loss of biodiversity and disease transmission caused by wild rodent populations. We previously showed that such a system of gene conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double-strand DNA break (DSB) is feasible in the female mouse germline. In the male germline, however, all DSBs were instead repaired by end joining (EJ) mechanisms to form an “insertion/deletion” (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homologydirected repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate gene conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient DSB formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of gene conversion and further increase the rate of “super-mendelian” inheritance from both male and female mice.
How sci-fi weapon could stop grey squirrels killing Britain’s trees
19723rymeradelle, INentertainment, 2021-12-23 12:41:06.
Grey squirrels pose the greatest threat to British foresters at the moment. They eat the bark of trees, leaving them to die. Picture: Grey squirrel perched on a tree It’s bad enough watching Britain’s ash trees wither from the ash dieback fungus now ravaging our countryside. We can only do so much. The squirrel is an exception to this rule. And it’s not just trees which are paying the price. This pest kills songbirds, and also pinches nests. Worse still, our native red squirrel, which once roamed the entire country — without chewing trees to death — is now an endangered species, clinging on in pockets of Scotland and places such as the Isle of Wight. The number of people living in the area is estimated to be around 200,000. Red Squirrel Survival Trust will make an announcement next month, with Red Squirrel Day on January 21. Its patron, the Prince of Wales, loves the vanishing red so much that he has a squirrel-feeding table in the hallway at Birkhall, his home on the Balmoral estate (where he has also erected ‘Squirrel Crossing’ road signs).
Scientists Used CRISPR Gene Editing to Choose the Sex of Mouse Pups
19906S. Fan, Singuarity Hub, 2021-12-23 08:37:01.
“Do you want a boy or a girl?” can be an awkward question.But in certain circles, it’s a question that’s asked every day. Take agriculture. In a perfect world, most cows would only birth females. Chicks would grow up to be all hens. “Sexing” a farm animal when they’re at a young age wouldn’t be a thing—especially when it means male animals, without the ability to produce milk or eggs, are often culled at a young age to preserve resources. There might be a better way. This month, a team tapped into the power of CRISPR to control the sex of the offspring in mice. By splicing CRISPR components into the parents’ genome, the team was able to flip on—or off—a switch that nearly perfectly determined the sex of their litters. Unlike previous attempts, the baby mice could go on to have litters of their own of both sexes. The targeted gene used for the edit is conserved across evolution, suggesting the technique could work in more animals than just mice. But it’s controversial. Essentially, the technique selectively kills off embryos of a certain sex, which immediately raises ethical red flags. For now, scientists aren’t concerned about the technology being used in humans due to its complexity. But the study is the latest to showcase biotech’s increasing ability to manipulate reproduction.
Weakly deleterious natural genetic variation amplifies probability of resistance in multiplexed gene drive systems
19904B. S. Khatri and A. Burt, bioRxiv, 2021.12.23.473701. 2021-12-23 08:31:18.
Evolution of resistance is a major barrier to successful deployment of gene drive systems to suppress natural populations. Multiplexed guide RNAs that require resistance mutations in all target cut sites is a promising strategy to overcome resistance. Using novel stochastic simulations that accurately model evolution at very large population sizes, we explore the probability of resistance due to three important mechanisms: 1) non-homologous end-joining mutations, 2) single nucleotide mutants arising de novo or, 3) single nucleotide polymorphisms pre-existing as standing variation. If the fraction of functional end-joining mutants is rare, we show that standing variation dominates, via a qualitatively new phenomenon where weakly deleterious variants significantly amplify the probability of multi-site resistance. This means resistance can be probable even with many target sites in not very large populations. This result has broad application to resistance arising in multi-site evolutionary scenarios including the evolution of vaccine escape mutations in large populations.Competing Interest StatementThe authors have declared no competing interest.
Interaction Between Entomology and Gene Technology: Bt-transgenic and Gene Drives for Pests Control .
20105J. C. Ndayıragıje, T. Özek, H. Çevik and İ. Karaca, Türk Bilim ve Mühendislik Dergisi, 3:108-115. 2021-12-22 17:00:56.
Pest control is the major agricultural activity for increasing crop productivity thus insuring food security. Recent pest management programs are depending too much on chemical pesticides, which are a threat to our health and environment. One of the greatest entomological achievements for the benefits of plant protection is the use of Bacillus thuringiensis to produce transgenic plants resisting pests. However, such organisms comprise inconveniences against human health and biodiversity in terms of genetic pollution. In many countries, the use of Genetically Modified Organisms is prohibited. This study review on integration of growing gene technology with actual scientific achievements can help to determine a sustainable solution to the pest’s problem. In this way, many literatures were referred on to comparatively criticize the effectiveness, safety and sustainability of gene drive over Bt transgenic based on scientific soundness. Gene drive technology is a new technic consisting of gene engineering and on-field monitoring of its transgenes. The case in point is the inappropriateness of Bt-transgenes. Practically, gene drive can be an alternative to Bacillus thuringiensis in pest control for increased safety and environmental protection.
Driving the Self-Destruction of Malaria-Transmitting Mosquitos
19948H. Aliouche, News Medical Life Sciences, 2021-12-22 09:36:57.
Self-destruction of malaria-transmitting mosquitoes can be driven by gene drives deployed to manipulate natural populations. In particular, they can be used to reduce the number of individuals in a population or to modify their composition; this is particularly useful when such species are vectors of disease. The use of genetic engineering tools is becoming increasingly widespread and enables the deployment of natural and synthetic gene drivers that can propagate a particular subset of genetic expressions population through the biasing of Mendelian inheritance laws.
Perspectives into Genetic Manipulations for Control of Dengue Vector (Aedes aegypti Linnaeus, 1762) with Reference to Progress in Indian Experiments
19975R. Chatterjee, S. Bhattacharya and B. K. Tyagi, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:46:45.
Vector-borne diseases like malaria, dengue, chikungunya, Japanese encephalitis, Zika and others claim millions of lives across the globe annually, and as such their control has become an ardent necessity. Past attempts over the decades have introduced vector control through chemical, biological and environmental means. However, these measures, already in place, failed to completely bring down the mortality rates from vector-borne diseases, most of which lack a vaccine to prevent epidemics or even a specific antidote to treat patients. The modern development of technologies such as the release of insects carrying a dominant lethal (RIDL) gene system, an example of transgenesis; the Wolbachia-based cytoplasmic incompatibility inducing infertility in female insects, an example of paratransgenesis; and the revolutionary gene drive (CRISPR/Cas9) technology, has their roots in the sterile insect technology (SIT), which worked by creating sterilized males through irradiation to compete with their wild counterparts and subsequently mate with females in nature to produce infertile eggs; a technology meant to gradually and finally exterminate the vector population in nature. These technologies have shown great promise, albeit many imperfections, particularly regarding acceptance by the concerned societies. As far as vector control is concerned, we have attempted to simplify their definitions for the common man so that the intricate scientific jargon about these technologies do not instill any fear or doubts to the end users.
Advances in Aedes Mosquito Vector Control Strategies Using CRISPR/Cas9
19929P. D. S. U. Wickramasinghe, G. N. Silva, Y. I. N. Silva Gunawardene and R. S. Dassanayake, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:39:52.
Advancements in genetic engineering have resulted in the development of mosquitoes with impaired vector competence, thereby limiting acquisition and transmission of pathogens. The main dengue (DENV) vector, Aedes aegypti, is an invasive species that have spread unwittingly across the world as a result of human trade and travel. The Ae. aegypti mosquito species has spread across tropical and subtropical regions, with higher presence in urban regions where rapid breeding patterns have shown in artificial containers. Identification of and treating an adequate number of mosquito breeding sites as a control measure have been done for the past couple of years, and yet improvement is far from the expectations, even with well-funded and well-organized initiatives. In order to stop the pathogen transmission, genetically modified mosquitoes (GMM) needs to be created and released. Despite many Aedes-related achievements, GMM creation has been challenging. The spread of particular genetic elements that impair vector competence, trigger deleterious recessive mutations, or skew a population's sex ratio can be used to prevent the spread of vector disease, or eradicate invasive organisms in a species-specific and eco-friendly manner. In recent years, genome editing strategies have evolved to make use of a variety of nucleases, ranging from sequence-specific zinc finger nucleases to modular TALENs (transcription activator-like effector nucleases) and most recently, RNA-guided nucleases adapted from bacterial adaptive immune systems, dubbed CRISPR/Cas (clustered regularly interspaced palindromic repeats/CRISPR associated systems). By combining these methods, a new era in gene editing had emerged. Generally, both of these gene editing technologies utilize sequence-specific nucleases to generate double-stranded DNA breaks (or nicks) in the target sequence, resulting in desired DNA modifications using endogenous DNA repair mechanisms. Since cells with DNA lesions are unable to divide further, the nuclease-generated strand breaks must be rapidly repaired by the cell to maintain the viability. CRISPR/Cas has been widely accepted for use in a variety of organisms, including insect species, with only minor optimization steps needed thus far. CRISPR/Cas9 technology transformed the process of engineering nucleases capable of cleaving complex genomic sequences. A complementary guide RNA (gRNA) directs the Cas9 endonuclease's operation to the specific DNA target site, enabling the editing of virtually any DNA sequence without complex protein engineering and selection procedures. Apart from genome editing, the specificity and flexibility of the CRISPR/Cas9 method enables unprecedented rapid development of genetically modified organisms with mutation systems for disease vector insect control. The stability and expression of the gene construct generated by CRISPR/Cas9 or any other method must be addressed before GMM are released, in order to make sure that pathogen transmission and formulation are interrupted robustly and completely. Spreading foreign antipathogen genes through gene drive strategies among wild mosquito populations strengthens the case for a more streamlined approach. Major fields that must be adequately assessed include risk evaluation and management, conducting studies to ensure human and environmental protection, developing effective control strategies built on comprehensive gene-driving systems, and adequately addressing the ethical, legal, and social consequences of GMM release. Although GMM is theoretically feasible as a disease control method, field releases should be made only when strong scientific evidence of human and environmental protection and effectiveness are presented, and public acceptance is addressed appropriately. This chapter discusses the diverse technological advances in generating Ae. aegypti mosquitoes which are resistant to dengue virus (DENV) and other diseases, as well as the biosafety and risk assessment of these procedures. Additionally, the chapter outlines a convincing path forward for developing successful genetic-based DENV control strategies based on CRISPR/Cas9, which could be expanded to control other arboviruses while maintaining biosafety.
Field Trials of Gene Drive Mosquitoes: Lessons from Releases of Genetically Sterile Males and Wolbachia-infected Mosquitoes
19925J. M. Marshall and V. N. Vásquez, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:27:08.
The discovery of CRISPR-based gene editing and its application to homing-based gene drive has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. At the same time, CRISPR-based gene editing has enabled a range of self-limiting gene drive systems to be engineered with much greater ease, including (1) threshold-dependent systems, which tend to spread only when introduced above a certain threshold population frequency, and (2) temporally self-limiting systems, which display transient drive activity before being eliminated by virtue of a fitness cost. As these CRISPR-based gene drive systems are yet to be field-tested, plenty of open questions remain to be addressed, and insights can be gained from precedents set by field trials of other novel genetics-based and biological control systems, such as trials of Wolbachia-transfected mosquitoes, intended for either population replacement or suppression, and trials of genetically sterile male mosquitoes, either using the RIDL system (release of insects carrying a dominant lethal gene) or irradiation. We discuss lessons learned from these field trials and implications for a phased exploration of gene drive technology, including homing-based gene drive, chromosomal translocations, and split gene drive as a system potentially suitable for an intermediate release.
Arthropods of Medical Importance: Need for Genetic and Other Innovative Vector Control Technologies, with Emphasis on Eco-biosocial and Environmental Considerations.
19923B. K. Tyagi, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:22:08.
Among the world’s known vector groups, viz. arthropods, snails and rodents, the most important vectors originate from arthropods, the jointed legs. Arthropods are doubtlessly regarded as the most dominant creatures on the Earth due largely to their remarkable structural and behavioural diversity, besides humongous species preponderance. Of course, some of these arthropods are serious pests and/or vectors of human and animal diseases—deadly, debilitating and economy destructing. According to an estimate, arthropod species make approximately 80% of the global biological diversity. Born some 350–400 million years ago, they have of course achieved, to the utter envy of all other animal forms, a formidable genetic diversity and robustness so much so that they have virtually captivated pivotal human attention for centuries. They serve as a spectacular model of bioprospecting or laboratory experiments mostly because they are found in abundance, breed prodigiously and are exceptionally easier to culture or cultivate. For the aforesaid reasons, arthropods are also the easy target for genetic manipulations such as the transgenesis (using the release of insect carrying dominant lethal (RIDL) gene system or gene drive-based genome editing, e.g. CRISPR/Cas9, to suppress or replace the vector population) or paratransgenesis (e.g. deploying endosymbiont Wolbachia-induced cytoplasmic incompatibility for replacing natural vector population). In particular, the advent of CRISPR technology has excited the potential to engineer new game-changing technologies and innovative systems that can be used to control wild populations of mosquitoes. Two developments of particular interest are a self-limiting system termed precision-guided sterile insect technique (pgSIT) and a homing-based gene drive (HGD). The unique features of these systems can make them valuable tools to control vector mosquitoes in the future. All these biotechnological advancements in vector control are designed to fit well in the multi-methodical integrated vector management (IVM) strategy.
Genetically Modified and other Innovative Vector Control Technologies
19912B. K. Tyagi, SpringerLink, 2021-12-21 08:48:19.
This book comprehensively covers the latest development in developing and deploying the genetically modified vectors, particularly Anopheles and Aedes mosquitoes responsible for transmitting malaria parasites and dengue viruses, the most deadly and/or debilitating among all the vector-borne diseases. It is considered timely and commensurate to bring about a book dealing with the various ecological, biological and social as well as regulatory aspects for the deployment of genetically modified vectors in special context with the biosafety of humans, his associates, and the environment. Written by an array of specialists and experts in various subjects of genetically modified organisms, this book centrally addresses the (i) basic principles of the genetic manipulation of vectors and they are potential impact on human and the environment, (ii) ecological, biological, ethical, legal and social implications of the use of genetically modified vectors, (iii) identification of potential hazards; assessment and management of risks for human and environment; risk/benefit analysis, (iv) principles and practices for the assessment and management of biosecurity and biosafety in laboratories (and in the field), (v) guiding principles for creation and management of institutional or national biosafety review boards and ethics review committees, and (vi) development and application of a biosafety regulatory framework and its related legal principles at national levels for securing the development and use of vector control methods based on genetic modification strategies.
Gene Drives For Malaria Control And Elimination
19693Annonymous, Health Tech, 2021-12-16 19:01:30.
There is notable ongoing research and prioritization of gene drive technology in Africa for Malaria control and elimination. Currently, there is ongoing gene drive mosquito research in Burkina Faso, Ghana, Mali and Uganda led by the Target Malaria consortium. While laboratory research has demonstrated that gene drive techniques are effective in altering the Anopheles mosquito populations so that they can no longer transmit Malaria parasites and crashing entire mosquito populations, this research still has a long way to go in testing the effectiveness of gene drive mosquitoes in controlling Malaria. Initiated in 2018, Target Malaria’s work in Uganda is led by the Uganda Virus Research Institute (UVRI). The work in Uganda is still in early stages, focusing on entomological mosquito collections from field sites on islands within Lake Victoria and mainland sites. In Burkina Faso, Target Malaria’s initiated exploratory gene drive research in in 2012, led by the Institut de Recherche en Sciences de la Santé (IRSS) in Bobo-Dioulasso. In 2019, the team released genetically modified sterile male mosquitoes in Bana village. The mosquitoes were genetically-modified to be sterile, which means they died without any offspring. These were not gene drive mosquitoes, and their release was not to test these as a vector control tool.
Gene Editing in the Wild: Shaping Decisions through Broad Public Deliberation
19701M. K. Gusmano, G. E. Kaebnick, K. J. Maschke, C. P. Neuhaus and B. C. Wills, The Hastings Center Report, 51. 2021-12-14 19:46:28.
The essays in this special report grew out of a project funded by the National Science Foundation (with NSF award number 1827935). Gregory E. Kaebnick and Michael K. Gusmano were co-principal investigators on the project, and Karen J. Maschke and Carolyn P. Neuhaus were coinvestigators. Ben Curran Wills was project manager and research assistant. Genetic editing technologies have long been used to modify domesticated nonhuman animals and plants. Recently, attention and funding have also been directed toward projects for modifying nonhuman organisms in the shared environment—that is, in the “wild.” Interest in gene editing nonhuman organisms for wild release is motivated by a variety of goals, and such releases hold the possibility of significant, potentially transformative benefit. The technologies also pose risks and are often surrounded by a high uncertainty. Given the stakes, scientists and advisory bodies have called for public engagement in the science, ethics, and governance of gene editing research in nonhuman organisms. Most calls for public engagement lack details about how to design a broad public deliberation, including questions about participation, how to structure the conversations, how to report on the content, and how to link the deliberations to policy. We summarize the key design elements that can improve broad public deliberations about gene editing in the wild.
The Decision Phases Framework for Public Engagement: Engaging Stakeholders about Gene Editing in the Wild
19643S. K. Barnhill-Dilling, A. Kokotovich and J. A. Delborne, Hastings Center Report, 51 Suppl 2:S48-s61. 2021-12-14 18:30:37.
Some experts and advocates propose environmental biotechnologies such as genetic engineering, gene drive systems, and synthetic biology as potential solutions to accelerating rates of species loss. While these tools may offer hope for a seemingly intractable problem, they also present potential governance challenges for which innovative decision-making systems are required. Two of the perennial governance challenges include, when are broader stakeholder groups involved in these decisions and who exactly should be involved? We propose the decision phases framework-which includes research and development, regulatory review, and deployment, management, and monitoring-as a framework for identifying which stakeholders might be best suited for different phases throughout the innovation and deployment of emerging environmental biotechnologies for species protection.
Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive
19623S. Gamez, D. Chaverra-Rodriguez, A. Buchman, N. P. Kandul, S. C. Mendez-Sanchez, J. B. Bennett, C. H. Sánchez, T. Yang, I. Antoshechkin, J. E. Duque, P. A. Papathanos, J. M. Marshall and O. S. Akbari, Nature Communications, 7202. 2021-12-10 21:34:38.
CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals.
Genomic insertion locus and Cas9 expression in the germline affect CRISPR/Cas9-based gene drive performance in the yellow fever mosquito Aedes aegypti
19603W. R. Reid, J. Lin, A. E. Williams, R. Juncu, K. E. Olson and A. W. E. Franz, bioRxiv, 2021.12.08.471839. 2021-12-08 18:56:04.
The yellow fever mosquito Aedes aegypti is a major vector of arthropod-borne viruses, including dengue, chikungunya, and Zika. A novel approach to mitigate arboviral infections is to generate mosquitoes refractory to infection by overexpressing antiviral effector molecules. Such an approach requires a mechanism to spread these antiviral effectors through a population, for example, by using CRISPR/Cas9-based gene drive systems. Here we report an autonomous single-component gene drive system in Ae. aegypti that is designed for persistent population replacement. Critical to the design of a single-locus autonomous gene drive is that the selected genomic locus be amenable to both gene drive and the appropriate expression of the antiviral effector. In our study, we took a reverse engineering approach to target two genomic loci ideal for the expression of antiviral effectors and further investigated the use of three promoters for Cas9 expression (nanos, β2-tubulin, or zpg) for the gene drive. We found that both promoter selection and genomic target site strongly influenced the efficiency of the drive, resulting in 100% inheritance in some crosses. We also observed the formation of inheritable gene drive blocking indels (GDBI) in the genomic locus with the highest levels of gene drive. Overall, our drive system forms a platform for the further testing of driving antipathogen effector genes through Ae. aegypti populations.Competing Interest StatementThe authors have declared no competing interest.
Modeling impact and cost-effectiveness of driving-Y gene drives for malaria elimination in the Democratic Republic of the Congo
19594N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, Evolutionary Applications, 2021-12-07 17:59:09.
Malaria elimination will be challenging in countries that currently continue to bear high malaria burden. Sex-ratio distorting gene drives, such as driving-Y, could play a role in an integrated elimination strategy if they can effectively suppress vector populations. Using a spatially explicit, agent-based model of malaria transmission in eight provinces spanning the range of transmission intensities across the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that include existing interventions such as insecticide-treated nets and case management of symptomatic malaria. Gene drive mosquitoes could eliminate malaria and were the most cost-effective intervention overall if the drive component was highly effective with at least 95% X-shredder efficiency at relatively low fertility cost, and associated cost of deployment below 7.17 $int per person per year. Suppression gene drive could be a cost-effective supplemental intervention for malaria elimination, but tight constraints on drive effectiveness and cost ceilings may limit its feasibility.
Gene editing used to create all-male or all-female litters of mice
19542J. Goodyer, Science Focus, 2021-12-06 20:26:39.
As males are unable to produce milk or lay eggs, the ability to breed cows and hens that produce all-female litters is likely to be high on most poultry and dairy farmers’ wish lists. Now, scientists at the Francis Crick Institute and the University of Kent have come a step closer to realising this goal after successfully using CRISPR gene editing techniques to produce all-female or all-male litters of mice. The technique could also be used to improve animal welfare in areas of scientific research in which only male or only female animals are required for studies, the researchers say. To make the breakthrough the researchers took advantage of the fact that CRISPR consists of two parts – the Cas9 enzyme, which cuts the DNA and enables scientists to alter specific regions of genes, and the guide RNA, which carries the Cas9 enzyme to the desired region on the genome.
Genetic conversion of a split-drive into a full-drive element
19540G. Terradas, J. B. Bennett, Z. Li, J. M. Marshall and E. Bier, bioRxiv, 2021.12.05.471291. 2021-12-06 20:21:27.
Gene-drive systems offer an important new avenue for spreading beneficial traits into wild populations. Their core components, Cas9 and guide RNA (gRNA), can either be linked within a single cassette (full gene drive, fGD) or provided in two separate elements (split gene drive, sGD) wherein the gRNA-bearing element drives in the presence of an independent static source of Cas9. We previously designed a system engineered to turn split into full gene drives. Here, we provide experimental proof-of-principle for such a convertible system inserted at the spo11 locus, which is recoded to restore gene function. In multigenerational cage studies, the reconstituted spo11 fGD cassette initially drives with slower kinetics than the unlinked sGD element (using the same Mendelian vasa-Cas9 source), but eventually reaches a similar level of final introgression. Different kinetic behaviors may result from transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.
The economic value of genetically engineered mosquitoes as a Malaria control strategy depends on local transmission rates
19788K. Lacy, K. A. Schaefer, D. P. Scheitrum and E. Y. Klein, Biotechnology Journal, 10. 2021-12-06 14:26:13.
This paper assesses the economic value of genetically engineered (GE) Anopheles gambiae mosquitoes as a malaria control strategy. We use an epidemiological-economic model of malaria transmission to evaluate this technology for a range of village-level transmission settings. In each setting, we evaluate public health outcomes following introduction of GE mosquitoes relative to a "status quo" baseline scenario. We also assess results both in contrast to-and in combination with-a Mass Drug Administration (MDA) strategy. We find that-in low transmission settings-the present value (PV) public health benefits of GE mosquito release are substantial, both relative to status quo dynamics and MDA. In contrast, in high transmission settings, the release of GE mosquitoes may increase steady-state infection rates. Our results indicate that there are substantial policy complementarities when GE mosquito release is combined with local MDA-the combined control strategy can lead to local eradication.
Gene editing used to create all-male or all-female mice litters
19502A. Reis, European Scientist, 2021-12-04 17:04:50.
Researchers from the Francis Crick Institute and the University of Kent used gene-editing technologies to create male-only and female-only mice litters, according to a study published in Nature Communications (1). The authors also suggested ways in which this method could be used to improve animal welfare in scientific research and agriculture. There are many situations in research and agriculture where it would be desirable to have just females or just males. For example, reproductive studies require only animals of the gender being studied, while in farming, egg and milk production needs only female animals. Sadly, in many cases, the unwanted animals end up being culled. “This work could have an immediate and valuable impact in scientific laboratories, as we’ve shown how it is safe and effective in mice, a common mammal used in medical and scientific research. While a lot of research needs both sexes, there are areas of study where only one is needed. For example, when studying the reproductive system, sex-specific diseases, or certain hormones”, said James Turner, group leader of the Sex Chromosome Biology Laboratory at the Crick says:
Gene-editing used to create single sex mice litters
19504The Francis Crick Institute, Phys Org, 2021-12-03 17:09:04.
Scientists at the Francis Crick Institute, in collaboration with University of Kent, have used gene editing technology to create female-only and male-only mice litters with 100% efficiency. This proof of principle study, published in Nature Communications today, demonstrates how the technology could be used to improve animal welfare in scientific research and perhaps also agriculture. In scientific research and also farming, there is often a need for either male or female animals. For example, laboratory research into male or female reproduction requires only animals of the sex being studied. And in farming, only female animals are required for egg production and in dairy herds. This means it is common practice for animals of the unrequired sex to be culled after birth. The researchers' new method uses a two-part genetic system to inactivate embryos shortly after fertilisation, allowing only the desired sex to develop. Such a genetically-based method to control the sex of offspring could drastically reduce culling in both industries. The embryo selection is based on the fact that there are two elements of CRISPR-Cas9—the Cas9 enzyme that cuts the DNA, allowing scientists to alter specific regions, and the guide RNA which carries the Cas9 to the right location on the genome. The team placed one element of the system on the father's X or Y chromosome, meaning that it will only be inherited by female or male embryos respectively. The other element is contributed by the mother, and is inherited by all embryos.
Single-sex mice litters were created with 100% efficiency using gene editing.
19498R. Silman, Brinkwire, 2021-12-03 17:00:12.
The Francis Crick Institute, in partnership with the University of Kent, has employed gene editing technology to construct 100% efficient female-only and male-only mouse litters. This proof-of-concept study, which was published today (Friday, December 3rd, 2021) in Nature Communications, shows how the technique could be used to improve animal wellbeing in scientific research and possibly agriculture. Male and female animals are frequently required in scientific research and husbandry. Laboratory research into male or female reproduction, for example, necessitates only animals of the examined sex. In addition, only female animals are needed for egg production and dairy herds in farming. This means that animals of the unrequired sex are routinely culled after birth.
Scientists eye gene drive technology to combat malaria
19496S. Buguzi, Sci Dev Net, 2021-12-03 16:55:44.
Scientists are hoping that adoption of gene drive technology could reduce mosquito populations as they call for new innovations in the fight against malaria, a fatal disease widespread in Sub-Saharan Africa. The World Health Organization (WHO) says the Africa region accounted for around 94 per cent of all global malaria cases and deaths in 2019. Over two-thirds of deaths were among children under the age of five. Gene drive technology — genetic engineering that modifies malaria mosquitoes so they can pass their genes on to large mosquito populations — could potentially contribute to malaria elimination in Africa, according to Krystal Birungi, a field entomology coordinator at the not-for-profit research consortium Target Malaria, Uganda. “There is a sense in which our best tools today are also our oldest, which implies that innovation needs to be scaled up.” Fredros Okumu, entomologist and director of science, Ifakara Health Institute, Tanzania “It is a cost-effective way to cut down malaria vectors, and is simple to implement because the mosquitoes themselves do the work,” said Birungi during a Roll Back Malaria Partnership virtual boot camp on malaria control innovation on 15 November. Although the technology is not on the market, and is yet to gain public acceptance, if rolled out it could complement existing malaria interventions such as insecticide-treated nets and indoor residual spray, helping reduce malaria cases, according to Birungi.
Lab animals: Gene-editing technology is used to create female-only and male-only mice litters
19493todayuknews, Today UK News, 2021-12-03 16:50:32.
Single-sex litters of mice — comprising only either female or male pups — have been produced by means of so-called CRISPR-Cas9 gene editing technology. The technique, developed by experts at the Francis Crick Institute and the University of Kent, works by inactivating embryos of one sex shortly after fertilisation. It could be used to improve animal welfare in both laboratory and agricultural settings where, for various reasons, only female or male animals are needed. It is common for animals of the unrequired sex to be culled — a practice which could be drastically reduced by controlling the sex of the animals prior to birth. As the technique requires the genetic modification of both parents to work, however, the approach would not be suitable for forcing the sex of designer babies. Single-sex litters of mice — comprising only either female or male pups — have been produced by means of so-called CRISPR-Cas9 gene editing technology. Pictured: the mice that were bred to create single-sex litters. The black parts of their coat are caused by the genetically modified cells, while the white parts come from the non-modified parts of their genome
Gene editing produces all-male or all-female litters of mice
19491E. Pennisi, Science, 2021-12-03 16:41:41.
In some farmers’ ideal world, cows would birth only females, sows would bear no boars, and chicks would all grow up to be hens. Such sex ratios would stop them from killing millions of male animals, which don’t produce eggs or milk. Now, scientists are a step closer to this reality. Researchers have harnessed the gene editor CRISPR to produce litters of mice all of one sex. That’s a potential boon to agriculture and may offer a more immediate advantage in scientific research. “The paper shows a state-of-the-art solution to producing single-sex species,” with “impressive results,” says Ehud Qimron, a CRISPR expert at Tel Aviv University who was not involved with the work. The impact for lab animals may be huge. “In the past 5 years around 25,000 papers were published using mice in sex-specific research studies,” says study co-author James Turner, a molecular geneticist at the Francis Crick Institute. “If we could prevent the generation of the unstudied sex, the number [saved] would be in the hundreds of thousands.” Other methods exist to skew the male/female ratio of newborn animals. Scientists can sort sperm by the weight of the sex chromosome, or cause embryos of one sex to die before birth. In a study published 2 years ago, researchers using the gene editor CRISPR managed to produce altered mice in which four of five litters were all female.
CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes
19469C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, S. K. Mahadevaiah, O. A. Ojarikre, P. J. I. Ellis and J. M. A. Turner, Nature Communications, 12:6926. 2021-12-03 15:06:30.
Animals are essential genetic tools in scientific research and global resources in agriculture. In both arenas, a single sex is often required in surplus. The ethical and financial burden of producing and culling animals of the undesired sex is considerable. Using the mouse as a model, we develop a synthetic lethal, bicomponent CRISPR-Cas9 strategy that produces male- or female-only litters with one hundred percent efficiency. Strikingly, we observe a degree of litter size compensation relative to control matings, indicating that our system has the potential to increase the yield of the desired sex in comparison to standard breeding designs. The bicomponent system can also be repurposed to generate postnatal sex-specific phenotypes. Our approach, harnessing the technological applications of CRISPR-Cas9, may be applicable to other vertebrate species, and provides strides towards ethical improvements for laboratory research and agriculture.
CRISPR gene-drive systems based on Cas9 nickases promote super-Mendelian inheritance in Drosophila
19471V. Lopez del Amo, S. Sanz Juste and V. M. Gantz, bioRxiv, 2021.12.01.470847. 2021-12-02 15:07:14.
CRISPR-based gene drive systems can be used to modify entire wild populations due to their ability to bias their own inheritance towards super-Mendelian rates (>100%). Current gene drives contain a Cas9 and a gRNA gene inserted at the location targeted by the gRNA. These gene products are able to cut the opposing wildtype allele, and lead to its replacement with a copy of the gene drive through the homology-directed DNA repair pathway. When this allelic conversion occurs in the germline it leads to the preferential inheritance of the engineered allele; a property that has been proposed to disseminate engineered traits for managing disease-transmitting mosquito populations. Here, we report a novel gene-drive strategy relying on Cas9 nickases which operates by generating staggered paired-nicks in the DNA to promote propagation of the gene drive allele. We show that only when 5' overhangs are generated, the system efficiently leads to allelic conversion. Further, the nickase gene-drive arrangement produces large stereotyped deletions, providing potential advantages for targeting essential genes. Indeed, the nickase-gene-drive design should expand the options available for gene drive designs aimed at applications in mosquitoes and beyond.
Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila
19441G. Oberhofer, T. Ivy and B. A. Hay, Proceedings of the National Academy of Sciences, 118:e2107413118. 2021-12-01 20:58:01.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. As a consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition dependent, so too will be the survival of that population. To test this idea, we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts-ClvRdbe are shifted to 29 °C, death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in homing-based drive and to bring about suppression and/or killing of specific individuals in response to other stimuli.
Applying functional genomics to the study of lamprey development and sea lamprey population control
19946J. R. York, R. E. Thresher and D. W. McCauley, Journal of Great Lakes Research, 47:S639-S649. 2021-12-01 09:30:24.
Lampreys are one of the few survivors of an ancient lineage of jawless vertebrates and have become an important study organism in numerous disciplines in the biological sciences, including evolutionary biology, embryology, ecology, physiology and biomedicine. At the same time, however, lampreys have created economic and ecological problems due, primarily, to the invasion of parasitic sea lamprey (Petromyzon marinus) into the North American Great Lakes and consequent negative impacts on local fish populations. Barriers, trapping and lampricide treatments have reduced these impacts, but concern for habitat restoration, non-target effects and possible evolution of resistance to lampricides suggests the need to develop additional strategies that supplement current control measures. The advent of functional genomics, and in particular CRISPR/Cas9 genome editing, offers a molecular approach to this on-going problem. Here, we review the successful application of functional genetic, transcriptomic, and CRISPR/Cas9 genome editing technologies in lampreys to address basic research questions in the fields of evolutionary and developmental biology. We then describe how these tools may be repurposed for use by fishery and conservation biologists to approach the problem of invasive sea lamprey from a molecular-genetic perspective.
New Arthropod Containment Recommendations Provide Essential Guidance for Safety of Gene Drive Research
19467S. James and D. O’Brochta, The American Journal of Tropical Medicine and Hygiene, tpmd211148. 2021-11-30 14:49:53.
Gene drive technologies have not yet been field tested, however, there are no data on the possible environmental or health effects of releasing gene drive–modified organisms. For this reason, there have been widespread calls for additional guidance on risk assessment and management, and some have even proposed a moratorium on gene drive research until such guidance is in place. One immediate need has been for guidance on appropriate containment measures that researchers should follow when investigating gene drive–modified organisms, given that these are meant to spread their transgenes by inter breeding with compatible local species. For example, a 2020 survey of biosafety professionals revealed that the majority felt existing guidance was inadequate for making risk assessments and containment decisions regarding gene drive–modified arthropods. Lack of standard guidance can lead to uneven application of containment measures among institutions and decreased public confidence in the research. The American Committee of Medical Entomology (ACME)of the American Society of Tropical Medicine and Hygiene has responded to this need with the recent publication of an addendum to its widely influential Arthropod ContainmentGuidelines. The new addendum6provides specific recommendations on containment practices for arthropods modified with engineered transgenes capable of gene drive.
New molecular genetic techniques: regulatory and societal considerations
19403Nielsen, K. M., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 18:07:46.
A rapidly expanding toolbox of techniques available for genome editing provides the basis for a new continuum in types of modifications that can be introduced into a genome and blur the bimodal GMO vs. non-GMO (genetically modified organism) divide. Site-directed nucleases (SDN) are now used to modify existing nucleotides within genomes instead of adding recombined DNA as transgenes. Moreover, new gene drive approaches are in development based on SDNs. A number of potential drive applications have been reported, but uncertainties in trait stability and limitations in knowledge of the affected system at various temporal and spatial levels slow down their current uses. Adoption of new genome targeted technology takes place in a social context. The context will vary between countries and cultures, expressed in values, ethics, politics and priorities - that are translated into different regulatory approaches. Some developed products using new genome editing techniques clearly fall under internationally negotiated regulations of GMOs. However, other product outcomes of editing techniques challenge our current understanding and definition of GMOs. There is an urgent need for further research, for building international consensus and harmonizing regulatory approaches to facilitate categorization, predictability, transparency, trust and trade.
Genome editing and its applications for insect pest control: Curse or blessing?
19401Hacker, I. , and Schetelig, M. F, AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 18:00:39.
Gene and genome editing are described as cutting-edge research tools with the potential to tackle urgent global challenges in the management of agricultural pests and human disease vectors such as mosquitoes. The field is defined by the chances and challenges to interlink the disciplines of insect genomics, molecular biology, and pest control together with the need for clear risk assessment, policy development and public approval of the application of such novel technologies. The goal is to generate innovative and sustainable pest control solutions applied in the best interest for the environment and human society. Here, starting from available genome editing technologies, the current strategies and applications for insect pest control are discussed, including approaches to overcome the evolution of resistance alleles and other potential pitfalls to be expected from selective pressures resulting from gene drive applications. They are supplemented by views on regulatory, policy and ethical considerations that in our opinion will be necessary to define how the different tools can be used in the future in a safe and responsible way.
Procedurally Robust Risk Assessment Framework for Novel Genetically Engineered Organisms and Gene Drives
19376Kuzma, J., Regulation and Governance, 15:1144-1165. 2021-11-29 17:13:52.
In this article, a new framework for improving risk assessments of novel genetically engineered organisms (GEOs) is developed and applied. The Procedurally Robust Risk Assessment Framework (PRRAF) provides a set of principles and criteria for assessing and enhancing risk assessment protocols for GEOs under conditions of high uncertainty. The application of PRRAF is demonstrated using the case of a genetically engineered mosquito designed to kill its wild population and therefore decrease disease transmission. Assessments for regulatory approval of this genetically engineered insect fall short of several PPRAF criteria under the principles of humility, procedural validity, inclusion, anticipation, and reflexivity. With the emergence of GEOs designed to spread in ecosystems, such as those with gene drives, it will become increasingly important for regulatory agencies and technology developers to bolster their risk analysis methods and processes prior to field testing. PRRAF can be used as a flexible guide for doing so within a variety of institutional, regulatory, and governance contexts.
CRISPR-based gene drives for combatting malaria: Need for an early stage technology assessment.
19374Liebert, W., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 17:09:24.
The potential power of CRISPR-based gene drives makes it necessary to engage in science and technology assessment already in early stages of research and development. In order to argue for efforts to address this urgent need, gene drives to combat malaria-transmitting mosquitoes are discussed using the concept of prospective technology assessment. First, development risks are described, followed by considerations about anticipatable risks and irreversible consequences, as well as unforeseeable effects and uncertainties. Afterwards, fundamental problems in connection with the development of gene drives against malaria mosquitoes are raised. Opportunities for shaping technology are briefly discussed, before alternatives, in particular the World Health Organization's elimination strategy, are considered. Finally, several normative questions are put forward.
AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application
19371Hendrichs, J. Pereira, R., Vreysen, M. J. B., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 17:04:54.
The concept of area-wide integrated pest management (AW-IPM), in which the total population of a pest in an area is targeted, is central to the effective control of such populations through the integration of genetic, biological and other pest suppression technologies. Insect movement, occurring sometimes over long distances, is generally underestimated. As a consequence, most conventional pest management is implemented as a localized or field-by-field, un-coordinated action against segments of a pest population, not taking in consideration insect movement, resulting very often in an unsustainable spiral of insecticide application and eventual resistance of the pest against the used insecticides. On the other hand, an AW-IPM approach adopts a preventive rather than a reactive strategy, whereby all individuals of the pest population are targeted in time and space and selecting a time when the pest populations are more vulnerable (e.g. during certain times of the year when the population densities are naturally low), requiring in the longer term fewer inputs and resulting in more cost-effective and sustainable pest management. It involves a coordinated effort over often larger areas, including not only agricultural, but also natural and other areas with pest presence. By addressing these sources of reinfestation in the surroundings of the agricultural areas, satisfactory pest control is achieved in the whole area and fewer control actions are required. This new textbook on AW-IPM assembles a series of selected papers that attempts to address various fundamental components of AW-IPM, e.g. the importance of relevant problem-solving research, the need for essential baseline data, the significance of integrating adequate tools for appropriate control strategies, and the value of pilot trials, etc. Of special interest are the numerous papers on pilot and operational programmes that pay special attention to practical problems encountered during the implementation of insect pest control programmes. A significant number of contributions to this book resulted from oral and poster presentations at the Third FAO/IAEA International Conference on “Area-wide Management of Insect Pests: Integrating the Sterile Insect and Related Nuclear and Other Techniques”, which was successfully held from 22-26 May 2017 at the Vienna International Centre, Vienna, Austria. The conference was attended by 360 delegates from 81 countries and six international organization. However, the book contributions were selected beyond the work presented at the conference and a number of experts dealing mainly with action programmes were invited to present their work in this publication
Synthetic sex ratio distorters based on CRISPR for the control of harmful insect populations
19369Fasulo, B., Meccariello, A., Papathanos, P. A., and Windbichler, N., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 16:55:38.
Since the overall reproductive output of a population is typically determined by the fertility of its females, which are rate-limiting in gamete production, a successful way to genetically control a population should involve artificially biasing the sex ratio towards males. In male heterogametic species, this could be achieved by the expression of a transgene-encoded endonuclease during spermatogenesis that would target and "shred" the X chromosome at several loci. This would prevent the transmission of X chromosome bearing gametes to the progeny, generating only males. Recent developments in molecular and synthetic biology have provided genome editing tools with great potential to engineer the genome of different species. Given the targeting flexibility of CRISPR-based endonucleases, it may now be possible to test whether X chromosome shredding has the potential to become a universal strategy to genetically control a wide variety of insect pests, of both agricultural and public health relevance.
Podcast: Malaria Gene Drive
19474S. Hartley, S. Neema and C. Opesen, University of Exeter Business School, 2021-11-25 15:15:30.
Professor Sarah Hartley and her two colleagues in Uganda, Stella Neema and Chris Opesen discuss gene drive research for malaria control. Funded by British Academy and Wellcome trust, their work is to understand the social science challenges around the development of this kind of technology and to consider how governance and ethics should be managed when dealing with a scientific breakthrough such as this.
Propagation of seminal toxins through binary expression gene drives can suppress polyandrous populations
19953J. Hurtado, S. Revale and L. M. Matzkin, bioRxiv, 2021.11.23.469777. 2021-11-24 09:48:59.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.Competing Interest StatementThe authors have declared no competing interest.
Historical perspective and new avenues to control the myiasis-causing fly Cochliomyia hominivorax in Uruguay.
23386Fresia P, Pimentel S, Iriarte V, Marques L, Durán V, Saravia A, Novas R, Basika T, Ferenczi A, Castells D, Saporiti T, Cuore U, Losiewicz S, Fernández F, Ciappesoni G, Dalla-Rizza M and M. A., Agrociencia Uruguay, 25:e974. 2021-11-18 07:43:36.
Mosca de la bichera’ or simply ‘bichera’ are common names given in Uruguay and the region to the primary myiasis-causing species Cochliomyia hominivorax, the New World Screwworm (NWS) fly (Diptera: Calliphoridae). Myiasis happens when dipteran larvae infest live animals at least during some developmental phase to feed on host’s flesh and fluids. For the NWS fly it is mandatory that all three larvae phases develop on living tissues of warm-blooded vertebrates, including humans. Unsurprisingly, this parasitic behavior causes great profit losses to the livestock industry and is also considered a neglected public health issue. NWS is endemic from the tropics and subtropics of the Americas, but has been eradicated from North and Central America through a Sterile Insect Technique (SIT) based Area Wide – Integrated Pest Management (AW-IPM) program that lasted more than 50 years
Science Has Given Us the Power to Undermine Nature’s Deadliest Creature: Should We Use It?
19304E. Herold, leaps.org, 2021-11-16 13:32:15.
British biotech company Oxitec has engineered male mosquitoes to have a genetic "kill-switch" that could potentially crash the local population of Aedes aegypti, at least in the short-term. The modified males that are being released are intended to mate with wild females. Males don't bite; it's the female that's deadly, always seeking out blood to gorge on to help mature her eggs. After settling her filament-thin legs on her prey, she sinks a needlelike proboscis into the skin and sucks the blood until her translucent belly is bloated and glowing red. The kill-switch will ensure that the female offspring die before they reach maturity and thus, be unable to reproduce. Should a small number of them survive, they will be rendered unable to bite. The genetic modification means the proboscis, the sickle-like needle that pierces the skin, won't form properly. The idea is that the lack of females for the males to mate with, over a few generations, will collapse the local population of Aedes aegypti. The modified mosquitoes are the second genetically engineered insect to be released in the U.S. by Oxitec. The first was a modified diamondback moth, an agricultural pest that doesn't bite humans. But with the mosquitoes, there are many questions about the long-term effects on wild ecosystems, other species in the food chain, and human health. With the Keys initiative, there has been vociferous opposition from environmental groups and some local residents, but some scientists and public health experts say that genetically modified insects pose less of a risk than the diseases they carry and the powerful, indiscriminant pesticides used to combat them.
High-resolution in situ analysis of Cas9 germline transcript distributions in gene-drive Anopheles mosquitoes
19324G. Terradas, A. Hermann, A. A. James, W. McGinnis and E. Bier, G3-Genes Genomes Genetics, 2021-11-15 14:20:36.
Gene drives are programmable genetic elements that can spread beneficial traits into wild populations to aid in vector-borne pathogen control. Two different drives have been developed for population modification of mosquito vectors. The Reckh drive (vasa-Cas9) in Anopheles stephensi displays efficient allelic conversion through males but generates frequent drive-resistant mutant alleles when passed through females. In contrast, the AgNosCd-1 drive (nos-Cas9) in Anopheles gambiae achieves almost complete allelic conversion through both genders. Here, we examined the subcellular localization of RNA transcripts in the mosquito germline. In both transgenic lines, Cas9 is strictly coexpressed with endogenous genes in stem and premeiotic cells of the testes, where both drives display highly efficient conversion. However, we observed distinct colocalization patterns for the two drives in female reproductive tissues. These studies suggest potential determinants underlying efficient drive through the female germline. We also evaluated expression patterns of alternative germline genes for future gene-drive designs.
Gene drives in malaria control: what we need to know
19289R. Mudziwapasi, M. C. Changara, A. Ndudzo, T. Kaseke, F. Godobo, F. L. Mtemeli, R. Shoko, F. Songwe, S. Ndlovu and S. Sandra Mlambo, Biotechnology and Biotechnological Equipment, 35:1623-1631. 2021-11-15 13:42:40.
Gene drives are being used to enhance a DNA sequence?s likelihood of passing between generations via sexual reproduction. Gene drives can be deployed to manipulate natural populations. They can be used to suppress populations by reducing the number of individuals in a population or to modify populations. There are more than 3000 mosquito species in the world, some of which are vectors of diseases. Malaria is a typical disease whose vectors are mosquitoes. It affects mostly tropical countries. It kills many people annually, many of whom are children. Interventions currently in use, such as indoor residual spraying and mosquito nets, are proving insufficient to eradicate malaria. Gene drives can be used in different ways to control mosquito populations or to eliminate mosquito species, thereby reducing malaria cases and deaths. This can occur through population replacement or suppression. However, before the elimination of any mosquito species for malaria control, it is necessary to consider the effects of such an action. Additionally, there is a need to review the options available for the control of mosquitoes and to create awareness of the benefits and risks of such an action. This paper, therefore, looks at the role of mosquitoes in the environment, the methods of controlling mosquitoes and malaria and necessary considerations when using gene drives inter alia.
New developments in the field of genomic technologies and their relevance to conservation management
19273G. Segelbacher, M. Bosse, P. Burger, P. Galbusera, J. A. Godoy, P. Helsen, C. Hvilsom, L. Iacolina, A. Kahric, C. Manfrin, M. Nonic, D. Thizy, I. Tsvetkov, N. Veličković, C. Vilà, S. M. Wisely and E. Buzan, Conservation Genetics, 2021-11-11 16:22:03.
Recent technological advances in the field of genomics offer conservation managers and practitioners new tools to explore for conservation applications. Many of these tools are well developed and used by other life science fields, while others are still in development. Considering these technological possibilities, choosing the right tool(s) from the toolbox is crucial and can pose a challenging task. With this in mind, we strive to inspire, inform and illuminate managers and practitioners on how conservation efforts can benefit from the current genomic and biotechnological revolution. With inspirational case studies we show how new technologies can help resolve some of the main conservation challenges, while also informing how implementable the different technologies are. We here focus specifically on small population management, highlight the potential for genetic rescue, and discuss the opportunities in the field of gene editing to help with adaptation to changing environments. In addition, we delineate potential applications of gene drives for controlling invasive species. We illuminate that the genomic toolbox offers added benefit to conservation efforts, but also comes with limitations for the use of these novel emerging techniques.
Two years of laboratory studies on the non gene drive genetically modified sterile male mosquitoes concluded successfully in Mali
19224M. Coulibaly, Target Malaria, 2021-11-09 21:44:38.
The Target Malaria Mali team at the Malaria Research and Training Centre (MRTC) based at the University of Sciences, Techniques and Technologies of Bamako (USTTB) is proud to have been the first Malian research team to work on non gene drive genetically modified sterile male mosquitoes. The team has just published the results of the two years we spent studying these mosquitoes in our laboratory. Thanks to this research, we have gained new knowledge and developed cutting-edge skills in the areas of entomology, molecular biology and genetics, allowing us to sustain a colony containing both local and genetically modified mosquitoes. This research was made possible thanks to an authorisation from the Malian Ministry of Environment, Sanitation and Sustainable Development (MEADD) issued on 21 June 2019 to import a strain of non gene drive genetically modified sterile male mosquitoes and study them in a contained environment. Initially designed at Imperial College London1, the genetically modified mosquitoes were then tested at Polo d’Innovazione di Genomica, Genetica e Biologia (PoloGGB) in Terni, Italy, before being transported to Mali. The mosquito eggs arrived by plane on 4 September 2019. They were kept in the insectarium renovated by the Target Malaria project.
Genetic control of invasive sea lamprey in the Great Lakes
19270D. Ferreira-Martins, J. Champer, D. W. McCauley, Z. Zhang and M. F. Docker, Journal of Great Lakes Research, 2021-11-08 16:16:20.
The invasive sea lamprey was a significant factor in the collapse of fish stocks in the Great Lakes, and it continues to threaten the multi-billion-dollar fishing industry. Thus, substantial resources are invested annually on sea lamprey control. Current control strategies have reduced sea lamprey populations by up to 90%, but they are expensive and have some limitations, e.g., lamprey-specific biocides applied to larval habitat impact native lampreys, and physical barriers that block adult lamprey access to spawning habitat impede migration of other fishes. Therefore, genetic control options which offer a theoretically powerful and effective pest control tool are being explored, although they have uncertain sociopolitical support, especially given the need to protect sea lamprey in their native range in Atlantic drainages. Here, we present an overview of genetic approaches with potential for application to sea lamprey control in the Great Lakes. We classify these approaches into two major categories: self-limiting (heritable sex ratio ratchet, Trojan gene, split gene drive) and self-sustaining (gene drive-based sex ratio distortion, homing suppression gene drive, toxin-antidote gene drives, and modification-type gene drives to aid suppression). We describe the technical aspects, challenges, and potential application of each method, focusing on gene drives, a fast-evolving research area that was only a distant option for sea lamprey control in previous reviews. We conclude that, given the risk of undesired spread of deleterious alleles from the Great Lakes, self-limiting genetic control options and confined gene drives will likely be preferred over unconfined gene drive options for sea lamprey control.
Uncle Sam’s Dangerous Game
19218X. Ping, XINHUANET, 2021-11-07 21:33:52.
Since the very beginning, residents in Florida Keys doubted if the “self-limiting” gene of Genetically Modified (GM) mosquitoes brought and released there by Oxitec, a biotech firm, and approved by U.S. Environmental Protection Agency and Florida Keys Mosquito Control District (FKMCD), was as powerful as the company described. Oxitec said that the male Aedes aegypti mosquitoes carried a “self-limiting” gene that produces a fatal protein which can kill their female offspring. In this way, population of mosquitoes in FKMCD was expected to crash rapidly. But for many residents in Florida Keys, those GM mosquitoes were like a Trojan Horse: it was sent to their doorstep, without any notice in advance, but they did not know what could be hidden on the inside. In fact, this "horse" has already been sent to other places multiple times. Before 2021, when Oxitec started the GM mosquitoes experiment in Florida, the firm had already been testing their immature research in Brazil, Malaysia, and the Cayman Islands for a decade. Yet in 2019, scientists from Yale University found out that Oxitec’s technology might actually strengthen offspring of mosquitoes rather than kill them. Residents in Florida Keys therefore rejected the program, pointing out that the firm had not been forthright in telling them the possible health consequences of the experiment. The Florida Keys Environmental Coalition, a local voluntary organization, launched a petition with over 200,000 signatures against the Oxitec project.
Will freeing ourselves (forever) from mosquitoes soon be a realizable “dream”? Pros and cons of an epochal turning point – breaking latest news
19160Annonymous, Breaking Latest News, 2021-11-05 14:34:10.
Also true for a dangerous insect like the mosquito: due to the pathologies of which vector, such as the malaria, the dengue o la yellow fever, every year in the world about 800 thousand people die. There are therefore quite a few reasons to want to get rid of it, not just the itchy summer bites, and thanks to the technique developed by Professor Crisanti it would seem possible, in a not too distant future. It starts from a premise: Not that we want to get rid of all mosquitoes. There are around 3,500 species of mosquitoes and fortunately only a few transmit parasitic diseases such as malaria or others that cause diseases such as zika and dengue. So if I want to get rid of malaria I have to attack malaria. Traditionally this has been done with insecticides which have shown all their limits and dangers. These measures, which are apparently simple, require sustainability over time, require resources and political continuity. All this is missing today. Hence biotechnology, the idea of making mosquitoes themselves do this job. If we manage to modify the genetic characteristics of mosquitoes, we can theoretically create mosquitoes that do not reproduce or that do not transmit the infection.
New Zealand wants to get rid of stoats with genetic engineering
19157C. Weerasinghe, Cyber Layman, 2021-11-05 14:23:23.
The principle of the “gene drive” is to modify a specific gene in a group of specimens of a species and then let the gene spread throughout the population by inheritance, through reproduction. If, as in this case, the aim is to reduce the population of animals, for example, we can make sure that only males are born. New Zealand stoats are not the only animals on which the technique of “gene drive” is thought to be used: for example, there are similar plans for mosquitoes that transmit malaria. The first time the technique proved effective was in 2015, when it was tested on a population of fruit flies; then it was tested on some species of yeast, insects and mice (for which, however, the effectiveness of the technique has not yet been demonstrated), never on an animal as large as an ermine. New Zealand may be the first country to experience such a thing domestically.
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modeling study
19134S. Leung, N. Windbichler, E. Wenger, C. Bever and P. Selvaraj, bioRxiv, 2021.11.01.466856. 2021-11-03 14:42:23.
Genetically engineering mosquitoes is a promising new vector control strategy to reinvigorate the fight against malaria in Sub-Saharan Africa. Using an agent-based model of malaria transmission with vector genetics, we examine the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission and quantify the gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting. We evaluate the performance of two different gene drive systems: "classic" and "integral". Various transmission regimes (low, moderate, and high - corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare seeking, are also simulated. Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above approximately 80-90‰). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as approximately 50‰ and in high transmission regimes with transmission-blocking effectiveness values above approximately 80-90‰. Thus, a single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.Competing Interest StatementThe authors have declared no competing interest.
Modeling the efficacy of CRISPR gene drive for schistosomiasis control
19109R. E. Grewelle, J. Perez-Saez, J. Tycko, E. K. O. Namigai, C. G. Rickards and G. A. De Leo, bioRxiv, 2021.10.29.466423. 2021-11-01 14:51:40.
CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. While much effort has been spent developing gene drives in mosquitoes, gene drive technology in molluscs has received little attention despite the role of freshwater snails as obligate, intermediate hosts of parasitic flukes causing schistosomiasis -- a disease of poverty affecting more than 200 million people worldwide. A successful drive in snails must overcome self-fertilization, which prevents a drive's spread. Simultaneous hermaphroditism is a feature of snails -- distinct from gene drive model organisms -- and is not yet incorporated in gene drive models of disease control. Here we developed a novel population genetic model accounting for snails' sexual and asexual reproduction, susceptibility to parasite infection regulated by multiple alleles, fitness differences between genotypes, and a range of drive characteristics. We then integrated this model with an epidemiological model of schistosomiasis transmission and snail population dynamics. Simulations showed that gene drive establishment can be hindered by a variety of biological and ecological factors, including selfing. However, our model suggests that, under a range of conditions, gene drive mediated immunity in snails could maintain rapid disease reduction achieved by annual chemotherapy treatment of the human population, leading to long-term elimination. These results indicate that gene drives, in coordination with existing public health measures, may become a useful tool to reduce schistosomiasis burden in selected transmission settings with effective CRISPR construct design and close evaluation of the genetic and ecological landscape.Competing Interest StatementJT and EKON were seed funded by the Merck Innovation Cup 2016 for research on schistosomiasis, and previously employed as external consultants to the Global Health Institute of Merck (KGaA) which produces treatments for schistosomiasis. REG and GADL were partially supported by the National Science Foundation's grants DEB-2011179 and ICER-2024383.
Alternatives for mammal pest control in New Zealand in the context of concerns about 1080 toxicant (sodium fluoroacetate)
19067B. Warburton, C. Eason, P. Fisher, N. Hancox, B. Hopkins, G. Nugent, S. Ogilvie, T. A. A. Prowse, J. Ross and P. E. Cowan, New Zealand Journal of Zoology, 43. 2021-10-29 20:19:18.
The ongoing use of 1080 toxin for the control of mammal pests in New Zealand remains highly contentious. Several reviews over the last 25 years identified information gaps and areas of concern, both social and scientific. In this paper these areas of concern are discussed and the extensive scientific and social research that has been undertaken to clarify and address them is reviewed. Although there has been a major national investment in research aimed at finding an alternative to 1080, that has not yet been fully achieved because of low or inconsistent efficacy and/or low cost-effectiveness of alternatives, regulatory difficulties in obtaining approval for aerial delivery of any alternative, and toxic residue concerns. Finding an alternative that has similar efficacy while satisfying the demands for species-selectivity, no residues, and humaneness is a continuing challenge. The most promising prospect appears to be through understanding the genome of the target animals and opportunities for genetic manipulation, either by developing species-specific designer lethal toxicants based on genome mining, or by gene editing to develop non-lethal technologies. Both will require considerable time and funding for research, and considerable effort and engagement to address social and regulatory hurdles.
Containment Practices for Arthropods Modified with Engineered Transgenes Capable of Gene Drive Addendum 1 to the Arthropod Containment Guidelines, Version 3.2
19069American Committee of Medical Entomology, Vector-Borne and Zoonotic Diseases, 2021-10-28 20:19:33.
Responsible conduct of research is a cornerstone of rigorous scientific discovery. Institutional committees, independent advisory panels, and expert steering groups are among the frameworks in academia meant to provide guidance and assurances that research activities do not result in harm to the environment, research staff, or public safety. For research involving arthropods of public health importance, several documents currently exist to guide investigators in methodologies to consider for reducing risks from arthropod escape. However, to date, there has been no standardized set of recommendations on containment practices for arthropods modified with engineered transgenes capable of gene drive. This document is meant to serve as a practical reference to fill that gap. Recommendations outlined here address containment considerations when a risk assessment indicates a possibility of establishment of a new arthropod vector species or genetically modified arthropods in the local environment.
European Parliament adopts text on biodiversity, calls for no releases of gene drive organisms
19071Third World Network, TWN Biosafety Briefing, 2021-10-27 20:24:55.
Gene drive technologies, such as GM mosquitoes for the control of vector-borne diseases, pose serious and novel threats for the environment and nature, including irreversible changes to food chains and ecosystems, and losses of biodiversity, on which the world’s poorest depend for their livelihoods; therefore reiterates concern about the new legal, environmental, biosafety and governance challenges that might arise from the release of genetically engineered gene drive organisms into the environment, including for nature conservation purposes; reiterates that the free, prior and informed consent of IPLCs must be sought and obtained prior to the release of any technologies which may impact on their traditional knowledge, innovation, practices, livelihoods and use of land, resources and water; stresses that this must be done in a participatory manner involving all potentially affected communities prior to any deployment. Given that gene drive technologies raise concerns about the difficulties of predicting their behaviour, and that gene drive organisms could become invasive species; therefore considers that no releases of genetically engineered gene drive organisms should be permitted, including for nature conservation purposes, in line with the precautionary principle.
A Golden Menace
19202S. Moutinho, Science, 2021-10-21 14:46:14.
An even bigger catastrophe looms: the invasion of the Amazon and its tributaries, part of the largest drainage basin in South America, which spans eight countries and is one of the richest hot spots for biodiversity on the planet. Golden mussels have been documented in the Pantanal wetlands just 150 kilometers from the Téles Pires River, which flows into the Amazon basin and connects to the Tapajós River, a tributary of the Amazon.“It only takes one boat encrusted with the mussel to cross the wetlands for the invader to make a new home in an Amazon river,” says biologist Marcia Divina at the state-owned Brazilian Agricultural Research Corporation. If the invader spreads in the Amazon, it could wipe out native species that scientists have not even studied yet, she adds. “We can’t even calculate the size of the impact.”Despite a late and anemic government response, researchers funded largely by affected hydroelectric companies have developed new tools to track the mussels’ relentless advance. And some are looking to an aggressive form of genetic engineering to eradicate it. That untested strategy is still likely years from being ready to deploy, but scientists see few other ways to slow an invader so easily spread by human transit and trade.
Genome Editing Tools and Gene Drives: A Brief Overview (1st ed.).
19295R. Mudziwapasi, R. Chekera, C. Z. Ncube, I. Shoko, B. Ncube, T. Moyo, J. G. Chimbo, J. Dube, F. F. Mashiri, M. A. Mubani, D. Maruta, C. Chimbo, M. Masuku, R. Shoko, R. P. Nyamusamba and F. N. Jomane, CRC Press, 2021-10-21 14:20:34.
Genome-editing methods are becoming routine tools for molecular and cell biologists. Such tools include ZFNs, CRISPR, megaTALs and TALENs. These tools are revolutionizing the creation of precisely manipulated genomes to modify the characteristics of organisms or cells. Additionally, gene drives have altered the way we understand inheritance laws. They give us the ability to have total control of the inheritance of traits of choice and importance. This succinct volume summarizes the history, principles and applications – as well as the advantages and disadvantages – of each of these tools and various kinds of gene drives. The book is part of a program to produce books helpful to students and faculties of science at colleges and universities. This volume in the Pocket Guides to Biomedical Sciences series will help demystify these technologies. The book fills the gap between established conventional methods and the novel and exciting newly introduced tools of genome editing and gene drives. It will help young scientists understand the emerging genome-editing tools and gene drives, thereby promoting related research and adoption.
Ecological vulnerability analysis for suppression of Drosophila suzukii by gene drives
19082C. R. Lalyer, L. Sigsgaard and B. Giese, Global Ecology and Conservation, 32:e01883. 2021-10-17 20:44:52.
Synthetic gene drives are transgenic constructs that aim to bias heredity and thereby influence the characteristics and fate of populations regarding abundance and evolution. Aside from irreversible effects in ecosystems that could be triggered by the release of a gene drive, research on confinable drives or even the reversibility of gene drives is underway and shows first success under laboratory conditions. However, their effectiveness under realistic conditions is not entirely clear unless first test releases have taken place. Since a potentially irreversible intervention into ecosystems is created, a prospective assessment is needed. We present an approach of prospective ecological vulnerability analysis for the proposed control of the invasive pest Drosophila suzukii by using gene drives. The analysis considers the accidental spread of the gene drive to the native habitat of Drosophila suzukii, with a focus on Japan. It contains a mapping of potential impacts as a consequence of the suppression of the insect. Multiple cascading effects were identified including the potential spread of the gene drive in geographic range or potential hybridization with non-target species. Determining the vulnerability of an ecosystem requires information regarding specific characteristics at different organizational levels. The vulnerability analysis of an affected ecosystem will initially serve to identify gaps in knowledge. Reducing complexity and breaking down the potential events that might arise from a gene drive population suppression enables to better understand endpoints i.e. concrete effects. Three potential effects have been selected for a specific analysis of the vulnerability of populations and species. A high vulnerability was obtained for the suppression of non-target (native) populations of Drosophila suzukii as well as for a decrease in specialized parasitoid abundance. The paper proposes the outline of a comprehensive prospective approach to understand the susceptibility of an ecosystem to unintended and irreversible harm.
Gene drive and RNAi technologies: a bio-cultural review of next-generation tools for pest wasp management in New Zealand
19000S. Palmer, P. K. Dearden, O. R. Mercier, A. King-Hunt and P. J. Lester, Journal of the Royal Society of New Zealand, 1-18. 2021-10-14 15:09:43.
There is a global need for novel, next-generation technologies and techniques to manage pest species. We review work on potential step-changing technologies for large landscape (>1000 hectares) pest management of social Vespula wasps. We also review M?ori perspectives on these controls to gauge social and cultural acceptability to research, test and use of novel controls. Approaches discussed are the use of gene silencing (RNAi) and gene drives (CRISPR-Cas 9) involving genetic modification, which has potential for pest control but vary in feasibility, cost, benefits and off-target risks. RNAi may be better suited for wasp control in high-value cropping systems due to scaling inefficiencies. Gene drives offer potential for large-scale control but would require legislative and wide social deliberation due to their status as genetic modification. Both RNAi and gene drives will require consultation with tangata whenua. M?ori interest groups agreed that exotic wasps must be controlled and expressed aversion to non-targeted traditional control methods. We present a diversity of opinions in parallel with scientific research underscoring the need for continued dialogue with M?ori. Novel biotechnological controls must satisfy a broad range of social and cultural criteria, receive regulatory approval, along with being demonstrated as safe, selective, and cost-effective.
GeneConvene Global Collaborative Webinar Series | Decision and Analysis Tools for Complex Problems
18961Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2021-10-13 20:07:26.
The challenges associated with the multiple phases of testing and possible deployment of gene drive-containing organisms appear to have similarities to those associated with various aspects of invasive species management. Preventing unwanted spread of the target species as well as monitoring and surveillance over large spatial scales are just two. Managing invasive species depends on making decisions based on an incomplete and sometimes very limited understanding of the relevant community ecology and the ever-present risk of unintended consequences. Can the deep experiences of those involved in invasive species management be leveraged against challenges in the gene drive domain? This webinar series will begin to explore that question.
Modeling homing suppression gene drive in haplodiploid organisms
18986Y. Liu and J. Champer, bioRxiv, 2021.10.12.464047. 2021-10-13 14:35:58.
Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some potential target species are haplodiploid, in which males develop from unfertilized eggs and thus have only one copy of each chromosome. This prevents drive conversion, a substantial disadvantage compared to diploids where drive conversion can take place in both sexes. Here, we study the characteristics of homing suppression gene drives in haplodiploids and find that a drive targeting a female fertility gene could still be successful. However, such drives are less powerful than in diploids. They are substantially more vulnerable to high resistance allele formation in the embryo due to maternally deposited Cas9 and gRNA and also to somatic cleavage activity. Examining models of continuous space where organisms move over a landscape, we find that haplodiploid suppression drives surprisingly perform nearly as well as in diploids, possibly due to their ability to spread further before inducing strong suppression. Together, these results indicate that gene drive can potentially be used to effectively suppress haplodiploid populations.
Small-scale release of non-gene drive mosquitoes in Burkina Faso: from engagement implementation to assessment, a learning journey
18910L. Pare Toe, N. Barry, A. D. Ky, S. Kekele, W. Meda, K. Bayala, M. Drabo, D. Thizy and A. Diabate, Malaria Journal, 20:395. 2021-10-11 14:50:37.
This study provides a review of engagement activities relevant to field trials on non-gene drive genetically-modified mosquitoes as well as an assessment framework-using both qualitative and quantitative studies as well as an audit procedure. The latter was implemented to evaluate whether the release activities could proceed with the appropriate level of agreement from the community. RESULTS: This paper shows the importance of this first phase of work to innovate and learn about engagement processes for responsible research in the field of genetic approaches for malaria vector control. The function of these assessments is crucial for the learning agenda. The assessments demonstrated ways to increase understanding and ensure effective progress with field studies and, therefore, the pathway for responsible research.
Spatial modelling for population replacement of mosquito vectors at continental scale
18861N. J. Beeton, A. Wilkins, A. Ickowicz, K. R. Hayes and G. R. Hosack, bioRxiv, 2021.10.06.463299. 2021-10-06 18:41:08.
We explore transmission of the gene drive between the subspecies, different hybridisation mechanisms, the effects of both local dispersal and potential wind-aided migration to the spread, and the development of resistance to the gene drive. We find that given best current available knowledge on the subspecies’ life histories, an introduced gene drive system with typical characteristics can plausibly spread from even distant offshore islands to the African mainland with the aid of wind-driven migration, with resistance taking over within a decade. Our model demonstrates a range of realistic dynamics including the effect of prevailing wind on spread and spatio-temporally varying carrying capacities for subspecies. We thus show both the plausibility and importance of accounting for a wide range of mechanisms from regional to continental scales
Gene drive: a faster route to plant improvement
18859H. A. Siddiqui, T. Harvey-Samuel and S. Mansoor, Trends in Plant Science, 2021-10-06 18:24:37.
Gene drives for control of vector-borne diseases have been demonstrated in insects but remain challenging in plants. Theoretically, they could be transformative in speeding breeding programs and contributing to food security through providing novel weed control methods. Zhang et al. now report the possibility of implementing gene drive in plants for the first time.
Gene drive revolution: How genetically tweaked mosquitoes could tip the balance in the battle to contain malaria
18903F. Okumu, Genetic Literacy Project, 2021-10-06 14:24:37.
In 2016, a World Health Organisation (WHO) panel concluded that even with the best use of current approaches, there would still be 11 million malaria cases in 2050. What’s needed are longer-term integrated strategies to complement current methods. These may include large-scale environmental management to reduce Anopheles breeding, mosquito-proof homes, stronger health systems and public education focusing on disease prevention. Fortunately, new technologies are also being developed which could complement these strategies at lower cost and less effort. One particularly exciting example is the release of genetically programmed mosquitoes, which we call “protector mosquitoes”. Upon mating with wild mosquitoes they produce offspring that are either incapable of any further reproduction or unable to transmit malaria parasites.
Genome engineering in insects for the control of vector borne diseases
18875V. E. Hillary and S. A. Ceasar, Progress in Molecular Biology and Translational Science, 179:197-223. 2021-10-05 19:22:57.
Insects cause many vector-borne infectious diseases and have become a major threat to human health. Although many control measures are undertaken, some insects are resistant to it, exacerbated by environmental changes which is a major challenge for control measures. Genetic studies by targeting the genomes of insects may offer an alternative strategy. Developments with novel genome engineering technologies have stretched our ability to target and modify any genomic sequence in Eukaryotes including insects. Genome engineering tools such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and most recently discovered, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) systems hold the potential to control the vector-borne diseases. In this chapter, we review the vector control strategy undertaken by employing three major genome engineering tools (ZFNs, TALENs, and CRISPR/Cas9) and discuss the future prospects of this system to control insect vectors. Finally, we also discuss the CRISPR-based gene drive system and its concerns due to ecological impacts.
Towards CRISPR/Cas9-based gene drive in the diamondback moth Plutella xylostella
18867X. Xu, T. Harvey-Samuel, H. Siddiqui, J. Ang, M. A. E. Anderson, C. Reitmayer, E. Lovett, P. T. Leftwich, M. You and L. Alphey, bioRxiv, 2021.10.05.462963. 2021-10-05 19:03:11.
Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipterans, yeast and mice, for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. Here, we used endogenous regulatory elements to drive Cas9 and sgRNA expression in the diamondback moth, (Plutella xylostella), and test the first split-drive system in a lepidopteran. The diamondback moth is an economically important global agriculture pest of cruciferous crops and has developed severe resistance to various insecticides, making it a prime candidate for such novel control strategy development. A very high level of somatic editing was observed in Cas9/sgRNA transheterozygotes, although no significant homing was revealed in the subsequent generation. Although heritable, Cas9-medated germline cleavage, as well as maternal and paternal Cas9 deposition was observed, rates were far lower than for somatic cleavage events, indicating robust somatic but limited germline activity of Cas9/sgRNA under the control of selected regulatory elements. Our results provide valuable experience, paving the way for future construction of gene drive-based genetic control strategies in DBM or other lepidopterans.Competing Interest StatementThe authors have declared no competing interest.
Genetically-modified possums and all-in-one trapping machines: funding for new predator-free studies
18787A. Allott, stuff, 2021-09-24 13:32:23.
Research into possum genes and creating an all-in-one predator detecting, luring, and trapping machine are among a handful of projects to receive new funding to help bring them into reality. Predator Free 2050 has awarded $2.4 million in Jobs for Nature funding to six postgraduate and post-doctoral researchers from Otago, Canterbury, Lincoln and Auckland universities. University of Otago researcher Alana Alexander, who is trying to discover which genes are important for possums’ reproduction and survival, is one of them. “Gene drives seem very exciting, but they’re a genie in a bottle. We don’t really want possums in New Zealand, but they are part of the ecosystem in Australia, so making sure it’s contained would be really important.” Alexander said she wants people to understand the risks and benefits, so they can give informed consent when thinking about pest control down the line.
Weltnaturschutzunion sucht Position
18803Anonymous, Informationsdienst Gentechnik, 2021-09-22 19:07:43.
Die Weltnaturschutzunion IUCN will in den nächsten drei Jahren eine breite interne Diskussion führen, ob Gentechnik und Gene Drives im Naturschutz eingesetzt werden sollen. Mit diesem Beschluss ist der Versuch gentechnikfreundlicher Organisationen, mit Artenschutz-Argumenten neuen gentechnischen Verfahren die Tür zu öffnen, vorerst abgewehrt. Der 1948 gegründeten International Union for Conservation of Nature gehören über 1300 staatliche und nichtstaatliche Naturschutzorganisationn aus aller Welt an. Sie trafen sich Mitte September in Marseille zu ihrem Weltnaturschutzkongress und verabschiedeten dabei mit der Resolution Nummer 75 auch einen Fahrplan, um zu einer „IUCN-Politik zur synthetischen Biologie in Bezug auf den Naturschutz“ zu gelangen. Der Begriff synthetische Biologie umfasst dabei alle gentechnischen Verfahren, mit denen biologische Systeme künstlich konstruiert oder umgestaltet werden.
New report demands moratorium on gene drives
18792GM Watch, GM Watch, 2021-09-21 13:49:44.
To help the public understand what's at stake, the Germany-based NGO Save Our Seeds (SOS) has published a report, "Gene Drives: The New Dimension of Genetic Engineering", which can be downloaded as a pdf document. The report provides a scientifically founded overview of how gene drive systems work, their possible areas of application, and the scientific discussion about their risks. It summarises the status of legislation and regulation at the German, European and global levels and recommends urgent political measures. The report explains how gene drives could be used in agriculture – research is focused on controlling pests and weeds and reversing the herbicide resistance in weeds that was caused and exacerbated by the spread of GM herbicide-tolerant crops. Not coincidentally, the report also notes that gene drives could be employed as bioweapons – for example, to eradicate beneficial insects in a region. The report points out, "The US military‘s Defense Advanced Research Projects Agency (DARPA) is one of the largest funders of gene drive research and is financially involved in almost every gene drive research project."
Gene Drive Organisms: A new dimension of genetic engineering
18790V. Henn and M. Imken, Save Our Seeds, 2021-09-21 13:42:53.
Enabled by new genetic engineering techniques such as CRISPR/Cas9, so-called gene drives have been developed in recent years that enable humans to spread new genes throughout the genome of wild animal populations. Gene drives force the inheritance of newly introduced genes to be inherited by all offspring, even if this lowers the survival chances of the affected species. In the most extreme case, gene drive technology could drive an entire species to extinction or replace wild populations with genetically modified organisms.
Predicting the spread and persistence of genetically modified dominant sterile male mosquitoes
18680A. Ickowicz, S. D. Foster, G. R. Hosack and K. R. Hayes, Parasites and Vectors, 14:480. 2021-09-16 13:03:47.
Reproductive containment provides an opportunity to implement a staged-release strategy for genetic control of malaria vectors, in particular allowing predictions about the spread and persistence of (self-limiting) sterile and male-biased strains to be compared to outcomes before moving to (self-sustaining) gene-drive strains. In this study, we: (i) describe a diffusion–advection–reaction model of the spread and persistence of a single cohort of male mosquitoes; (ii) elicit informative prior distributions for model parameters, for wild-type (WT) and genetically modified dominant sterile strains (DSM); (iii) estimate posterior distributions for WT strains using data from published mark-recapture-release (MRR) experiments, with inference performed through the Delayed-Rejection Adaptive Metropolis algorithm; and (iv) weight prior distributions, in order to make predictions about genetically modified strains using Bayes factors calculated for the WT strains. If a single cohort of 5000 genetically modified dominant sterile male mosquitoes are released at the same location as previous MRR experiments with their WT counterparts, there is a 90% probability that the expected number of released mosquitoes will fall to < 1 in 10 days, and that by 12 days there will be a 99% probability that no mosquitoes will be found more than 150 m from the release location. Spread and persistence models should form a key component of risk assessments of novel genetic control strategies for malaria vectors. Our predictions, used in an independent risk assessment, suggest that genetically modified sterile male mosquitoes will remain within the locality of the release site, and that they will persist for a very limited amount of time. Data gathered following the release of these mosquitoes will enable us to test the accuracy of these predictions and also provide a means to update parameter distributions for genetic strains in a coherent (Bayesian) framework. We anticipate this will provide additional insights about how to conduct probabilistic risk assessments of stage-released genetically modified mosquitoes.
Faut-il miser sur le forçage génétique contre les espèces invasives?
18933P. Minet, Le Temps, 2021-09-12 19:51:46.
Un «gene drive» peut servir à annihiler complètement et rapidement une population d’animaux indésirables. Prometteuse pour lutter contre les espèces invasives, cette technologie a fait l’objet d’âpres débats dans le cadre du congrès mondial de la nature à Marseille. Cela peut paraître paradoxal: dans certaines situations, la protection de la biodiversité passe par l’anéantissement d’une espèce. C’est le cas lorsque des écosystèmes fragiles sont confrontés à l’irruption d’un animal ou d’une plante originaire d’une autre zone géographique, et qui a le potentiel de détruire ou de supplanter les espèces locales. L’exemple typique est celui de nombreuses îles où des rats introduits par l’être humain déciment les oiseaux en mangeant leurs œufs.
To exterminate, or not to: Scientists debate tweaking wild genomes
18529French Press Agency, Daily Sabah, 2021-09-12 16:11:31.
veryone remembers Jeff Goldblum's famous speech in 1993 classic Jurassic Park: “Your scientists were so preoccupied with whether they could, they didn't stop to think if they should.” Well, these scientists are debating whether one should. In the movie, reconstructing and tweaking genetic material had made it possible to bring dinosaurs back to life. Today, a technology that manipulates animal genomes, called gene drive, has become a reality. The goal, however, is not to revive long-gone species, but to eliminate invasive ones. Steven Spielberg's film was set on an imaginary island off the coast of Costa Rica, and it is also on an island that the first open-air experiments in programmed extinction could take place, according to experts gathered at the International Union for the Conservation of Nature (IUCN) Congress in Marseille. It could happen within a decade, they told Agence France-Presse (AFP). That's because fragile island ecosystems are in crisis. Dozens of vertebrate species have vanished in the last century, and dozens more are on a glide path to extinction. The culprits are non-native rats, snakes and mosquitoes – all introduced by humans, for the most part by accident – that eat bird eggs, infect birds with disease, or outcompete indigenous amphibians and mammals. For more than 20 years, Island Conservation has been working to eradicate rodents and other invasive alien species, which are a major threat to biodiversity globally, the organization's Royden Saah told AFP. The conservation NGO has been successful on two Galapagos islands – Seymour North and Mosquera – using traps and poison-delivering drones. But species eradication using these tools is costly and has no guarantee of success. Rat poison is effective, but poses risks to other species.
Scientists debate promise, peril of tweaking wild genomes
18517J. Zamora, Phys Org, 2021-09-11 14:53:57.
In the movie Jurassic Park, reconstructing and tweaking genetic material makes it possible to bring dinosaurs back to life. Today, a technology that manipulates animal genomes, called gene drive, has become a reality. The goal, however, is not to revive long-gone species, but to eliminate invasive ones. Steven Spielberg's film was set on an imaginary island off the coast of Costa Rica, and it is also on an island that the first open-air experiments in programmed extinction could take place, according to experts gathered at the International Union for the Conservation of Nature (IUCN) Congress in Marseille. It could happen within a decade, they told AFP. That's because fragile island ecosystems are in crisis. Dozens of vertebrate species have vanished in the last century, and dozens more are on a glide path to extinction. The culprits are non-native rats, snakes and mosquitoes—all introduced by humans, for the most part by accident—that eat bird eggs, infect birds with disease, or outcompete indigenous amphibians and mammals.
The viral era
18352B. Giese, EMBO reports, 22:e53229. 2021-09-06 13:54:36.
New biotechnologies such as gene drives and engineered viruses herald a viral era that would give humans exceptional power over any organism at the level of the genotype. In synthetic biology, orthogonality—in the sense of lack of interference—between different systems or system components is sought for new creations. Current approaches to controlling gene drives also aim for orthogonality, but at a higher level of organisms, populations and species. To keep information under control, orthogonality and reversibility have to be guaranteed before any releases. As with chemical substances, where persistence and bioaccumulation are reasons for concern, the same should apply to genetic information released into nature
$1M in funding for project to cull mouse plagues
18349K. Brown, University of Adelaide NEWSROOM, 2021-08-31 13:47:59.
South Australian researchers are set to use genetic tools to help find innovative solutions to the devastating mouse plagues that have caused massive economic damage to Australian farmers.The University of Adelaide has been awarded $1 million in funding from the South Australian Government’s Research and Innovation Fund (RIF), to undertake the ground-breaking Genetic Biocontrol Technology for Invasive Pests, or Gene Drive, project, in conjunction with the Department for Environment and Water.Researchers from the University of Adelaide will develop genetic strategies to suppress invasive rodents with maximum specificity and safety. The team will also conduct research to engage with stakeholders to understand community views and concerns.
Gene drive escape from resistance depends on mechanism and ecology
18261F. Cook, J. J. Bull and R. Gomulkiewicz, bioRxiv, 2021.08.30.458221. 2021-08-31 13:20:26.
Gene drives can potentially be used to suppress pest populations, and the advent of CRISPR technology has made it feasible to engineer them in many species, especially insects. What remains largely unknown for implementations is whether anti-drive resistance will evolve to block the population suppression. An especially serious threat to some kinds of drive is mutations in the CRISPR cleavage sequence that block the action of CRISPR, but designs have been proposed to avoid this type of resistance. Various types of resistance at loci away from the cleavage site remain a possibility, which is the focus here. It is known that modest-effect suppression drives can essentially `outrun' unlinked resistance even when that resistance is present from the start. We demonstrate here how the risk of evolving (unlinked) resistance can be further reduced without compromising overall suppression by introducing multiple suppression drives or by designing drives with specific ecological effects. However, we show that even modest-effect suppression drives remain vulnerable to the evolution of extreme levels of inbreeding, which halt the spread of the drive without actually interfering with its mechanism. The landscape of resistance evolution against suppression drives is therefore complex, but avenues exist for enhancing gene drive success.Competing Interest StatementThe authors have declared no competing interest.
Genetically changed mosquitoes could transform Africa’s long fight against malaria
18258L. Singh, ForumIAS, 2021-08-30 13:13:44.
In nature, there’s a phenomenon called gene drive which operates in the process of reproduction. This is when a genetic element is able to increase the chance that it will be inherited by offspring. The general underlying principle of all gene drives is an organism that will produce offspring similar to themselves. Some characteristics are randomly passed on from parents to the next generation. However, gene drive forces a different type of inheritance that ensures a specific characteristic is always present in the next generation. Scientists engineer gene drive using various molecular tools. Gene drive is not just a human invention; some occur naturally in insects. Unlike traditional genetic modification, gene drives enable extremely rapid spread of the desired characteristics.
The international governance of gene drive organisms
18320F. Rabitz, Environmental Politics, 2021-08-29 13:07:16.
Gene Drive Organisms (GDOs) are a proposed biotechnological intervention that might generate significant benefits for the conservation and sustainable use of biological diversity while also raising critical biosafety issues. Despite their inevitable transboundary effects, their implications for international institutions remain undertheorized. This text develops a theoretical analysis of international GDO governance. First, it elaborates the problem-structural characteristics of GDOs that turn them into a novel and distinct governance challenge, focusing on leverage, cost-benefit distributions, irreversibility, as well as uncertainty and unpredictability. Second, it derives the implications of problem structure for institutional design by focusing on pre-release risk assessment and authorization, as well as post-release monitoring and liability. Third, it uses these institutional implications for benchmarking the Cartagena Protocol on Biosafety, the focal point in international biotechnology regulation, for effective GDO governance. The text concludes that institutional reforms are required for folding GDOs into international biodiversity policy.
Versatile Applications of the CRISPR/Cas Toolkit in Plant Pathology and Disease Management
19445M. S. Wheatley and Y. N. Yang, Phytopathology, 111:1080-1090. 2021-08-25 21:11:15.
New tools and advanced technologies have played key roles in facilitating basic research in plant pathology and practical approaches for disease management and crop health. Recently. the CRISPR/Cas (clustered regularly interspersed short palindromic repeats/CRISPR-associated) system has emerged as a powerful and versatile tool for genome editing and other molecular applications. This review aims to introduce and highlight the CRISPR/Cas toolkit and its current and future impact on plant pathology and disease management. We will cover the rapidly expanding horizon of various CRISPR/Cas applications in the basic study of plant-pathogen interactions, genome engineering of plant disease resistance, and molecular diagnosis of diverse pathogens. Using the citrus greening disease as an example, various CRISPR/Cas-enabled strategies are presented to precisely edit the host genome for disease resistance, to rapidly detect the pathogen for disease management, and to potentially use gene drive for insect population control. At the cutting edge of nucleic acid manipulation and detection, the CRISPR/Cas toolkit will accelerate plant breeding and reshape crop production and disease management as we face the challenges of 21st century agriculture.
CRISPR/Cas9-based functional characterization of the pigmentation gene ebony in Plutella xylostella
18155X. Xu, T. Harvey-Samuel, J. Yang, M. You and L. Alphey, Insect Molecular Biology, 2021-08-20 17:59:44.
Abstract Body pigmentation is an important character of insects in adapting to biotic and abiotic environmental challenges. Additionally, based on the relative ease of screening, several genes involved in insect melanisation have been used in classic genetic studies or as visual markers in constructing transgenic insects. Here, a homolog of the Bombyx mori melanisation-inhibiting gene ebony, associated with the conversion of dopamine to N-?-alanyl dopamine, was identified in a global pest, Plutella xylostella. The CRISPR/Cas9 system was applied to generate multiple Pxebony knockout alleles which were crossed to produce a Pxebony knockout strain, showing darker pigmentation in larvae, pupae and adults, compared with wildtype. Interestingly, we observed that Pxebony heterozygotes displayed an intermediate darkened phenotype, indicating partial dominance between the knockout and wildtype alleles. The fitness costs of Pxebony-deficiency were also assessed in the mutant strain, indicating that embryo hatchability and larval survival were significantly reduced, while the eclosion rate was not obviously affected. Our work provides a potential target for exploring CRISPR-based genetics-control systems in this economically important pest lepidopteran.
Africa must not rest until Malaria rests: What is the role of emerging technologies?
18165R. Oronje, AFIDEP, 2021-08-20 14:42:16.
As we mark the World Mosquito Day today, it is a sad reminder that Malaria still kills hundreds of thousands of people every year, majority of these people in Africa. According to the World Health Organisation (WHO), Malaria killed 409,000 people in 2019, and 94% of these deaths were in Africa. For those who survive the disease, they have many horrifying tales to tell because many get Malaria every so often, especially for those living in Malaria endemic regions. I have many horrifying tales of my experience with Malaria because I grew up in the Malaria-endemic region of Western Kenya. One of these tales is when I passed out in school when I was in Primary-4 because I had refused to take the very bitter Quinine tablets. My Mum was called to take me to hospital and by the time she arrived, I was in “hallucination mode” because all I remember is seeing two Mums lifting me up; and the next time I woke up, I was in a nearby health facility. My parents still live in this region, which means I visit them often and so every time I visit Western Kenya without taking prophylaxis, I can be sure I will come back with Malaria. But this blog is not about my horrifying Malaria tales, so I will not delve much more into that. Although many people in sub-Saharan Africa have suffered from Malaria, many are not aware of ongoing efforts to develop and test new tools with potential to eliminate Malaria. In a recent study by the African Institute for Development Policy (AFIDEP) on the “Landscape and Political Economy Analysis of Emerging Health Technologies in Sub-Saharan Africa”, we found that apart from the researchers developing these new tools and their funding agencies, other stakeholders including journalists, civil society actors, and policymakers know little, if anything, about the ongoing research on emerging health technologies, including those technologies being developed with potential to eliminate Malaria.
Insect pest management in the age of synthetic biology
18682R. Mateos Fernández, M. Petek, I. Gerasymenko, M. Juteršek, Š. Baebler, K. Kallam, E. Moreno Giménez, J. Gondolf, A. Nordmann, K. Gruden, D. Orzaez and N. J. Patron, Plant Biotechnology Journal, 2021-08-20 13:09:26.
Arthropod crop pests are responsible for 20% of global annual crop losses, a figure predicted to increase in a changing climate where the ranges of numerous species are projected to expand. At the same time, many insect species are beneficial, acting as pollinators and predators of pest species. For thousands of years, humans have used increasingly sophisticated chemical formulations to control insect pests but, as the scale of agriculture expanded to meet the needs of the global population, concerns about the negative impacts of agricultural practices on biodiversity have grown. While biological solutions, such as biological control agents and pheromones, have previously had relatively minor roles in pest management, biotechnology has opened the door to numerous new approaches for controlling insect pests. In this review, we look at how advances in synthetic biology and biotechnology are providing new options for pest control. We discuss emerging technologies for engineering resistant crops and insect populations and examine advances in biomanufacturing that are enabling the production of new products for pest control.
The Complex Lives of Mosquitoes: The Key for Malaria Control
18216F. Okumu, ISGlobal, 2021-08-19 15:19:27.
Mosquitoes spread diseases to millions of people around the world, yet they remain poorly understood by most. Studying their biology and behaviours can help us combat, and eventually eliminate, dangerous diseases such as malaria and dengue fever.There are nearly 3,500 species of mosquitoes. About 400 belong to a family called Anopheles, and of these, only about 50-70 can actually transmit malaria to humans. In Africa, where the malaria burden is highest, the most important are Anopheles gambiae, Anopheles funestus, Anopheles arabiensis and Anopheles colluzzi. Often, only one or two of these dominate malaria transmission in any country. Effective malaria control can therefore be achieved by simply identifying, understanding and then targeting just the one or two dominant Anopheles species instead of trying to kill all mosquitoes.A female Anopheles lays about 500 eggs in her lifetime, usually in standing fresh waters, although some breed along rivers or in brackish waters. The eggs weigh just 4 micrograms each and float like little pontoons on the water surfaces
Attack of the Superweeds
18153H. C. Brown, New York Times, 2021-08-18 17:55:25.
If there’s a plant perfectly suited to outcompete the farmers, researchers and chemical companies that collectively define industrial American agriculture, it’s Palmer amaranth. This pigweed (a catchall term that includes some plants in the amaranth family) can re-root itself after being yanked from the ground. It can grow three inches a day. And it has evolved resistance to many of the most common weed killers, continuing to reproduce in what ought to be the worst of circumstances: A three-day-old, herbicide-injured seedling, for example, can expend its last bit of energy to produce seeds before it withers up and dies. Unchecked, Palmer amaranth can suppress soybean yields by nearly 80 percent and corn yields by about 90 percent. Nicolet was ultimately allowed to spray dicamba last summer because he purchased it before restrictions took effect. He used it this year too: The Trump administration issued new approvals for some formulations containing dicamba just a week before the presidential election. Still, Nicolet says the weed killer will eventually stop working on his land, another management tool rendered useless by the pigweed’s remarkable onslaught. Whether that day is 10 years in the future or three, he has no idea, but the Palmer amaranth continues to gain ground all the while. This summer, a handful of pigweeds sprouted in a field that had recently been sprayed. Nicolet couldn’t weed the 96 affected acres by hand, so he decided to let them grow. “It’s not really enough to hurt yield this year,” he said. “But you know, you have 100 weeds out there, the next year you’ll have a million.”
Identifying Sites for Testing Modified Mosquitoes as a Strategy to Eradicate Malaria
18222A. Fell, UC Davis News, 2021-08-18 15:34:12.
In a newly published article in the journal Evolutionary Applications Professor Greg Lanzaro and his team at the Vector Genetics Laboratory, UC Davis School of Veterinary Medicine, set forth a framework for the selection of field sites in Africa best suited for testing genetically engineered mosquitoes (GEMs).“We followed earlier recommendations from the National Academy of Sciences and the World Health Organization that argued that a physical island would be a logical place to initiate early field trials of a GEM that uses gene drive technology,” Lanzaro said.n this paper, they establish a set of criteria including geographic and genetic isolation, biological complexity, island size, and topography and apply these criteria to a set of 22 potential island sites located off the coast of Africa. Their goal is to identify sites that maximize prospects for success, minimize risk, and serve as a fair, valid and convincing test of the efficacy and impacts of a GEM product intended for large-scale deployment in Africa.
New mosquito control tools are critical
18148L. Braack, Open Access Government, 2021-08-17 17:38:18.
Globally, we are making slow headway in the fight against malaria, but there has been progress, nonetheless. Since 2000, 39 countries and territories have managed to rid themselves of malaria; the most recent is China. Existing tools can achieve local elimination, but the battle is becoming harder and mosquitoes and parasites are able to change their defences, which is why we too have to constantly adapt and respond with better tools and strategies. We should also be on high alert; malaria has been distracting our attention from what will be our next global public health threat: mosquito-borne arboviruses such as Dengue, Chikungunya, Zika, Yellow Fever, West Nile Virus, Usutu, and a host of others few people have heard of. These arboviruses are spreading across the globe, each year more abundant. The mosquitoes that transmit them pose a different set of challenges, as most of them bite by day, with very different breeding habits. We must increase public awareness of the rising threat and invest much greater research effort to find ways to combat these viruses and mosquitoes.
Genetic modification could be used to combat invasive crayfish
18086O. Rudgard, The Telegraph, 2021-08-15 17:34:40.
Genetically-modified crayfish carrying infertility genes could be used to tackle the problem of invasive crustaceans in British waterways. A technique being developed by scientists at the University of Edinburgh's Roslin Institute offers hope for conservationists trying to tackle the problem of American crayfish invading UK rivers. "Gene drive" science, which involves altering the genetics of individuals of a certain species to spread desirable traits through a population, has been mooted as a possible solution to malarial mosquitoes and, in the UK, to the problem of invasive grey squirrels, where it would be used to spread infertility. Scientists are now suggesting the same technique as a potential solution to the problem of signal crayfish, a US species introduced to the UK in the 1970s that now poses a serious threat to Britain's native white-clawed crayfish.
Knowing and Controlling: Engineering Ideals and Gene Drive for Invasive Species Control in Aotearoa New Zealand
18025C. H. Ross, Nature Remade: Engineering Life, Envisioning Worlds, 2021-08-10 17:51:46.
On the islands of Aotearoa, also called New Zealand, invasive species have been a prominent and persistent concern for local ecosystems. Traditional methods of biological control, though, can be difficult to implement and often have harmful side- effects for the environment and human health. Recent developments in genetic engineering have led to the creation of a new technology called gene drive, which some have suggested may pro-vide a safer, easier alternative way to “restore damaged ecosystems and save endangered wildlife by genetically removing invasive species.” 1 While the promises of gene drive for invasive species control have attracted the attention of many in Aotearoa New Zealand interested in preserving or restoring the islands’ native environment, at the same time it has prompted calls for caution regarding their controllability and possible unintended consequences of their use. 2 However, the consideration of gene drive for the control of invasive species in Aotearoa New Zealand is more than just an issue of a controversial use of emerging biotechnology. At stake also are critical questions about what it means to know and control life. What are the kinds of knowledge that enable and underwrite the notions of controlling of life? If gene drive confers the power to control inva-sive species, who decides whether and how that control is exercised and with what responsibilities? And, crucially, what visions of the world are embedded in the aspirations of scientifically knowing and technologically controlling life?Controlling life has long been a central aspiration of the biological sciences. In the early twentieth century, aspirations to greater control over life manifested in rigorous laboratory experimentation, attempts to engineer organisms to be more amenable to human purposes, and explanatory commitments to a mechanistic conception of life. 3 Mechanistic approaches have been ubiquitous in biological practice aimed at bringing living things and their functions into the purview of human intention and volition by isolating, manipulating, and better understanding the function of more fundamental parts. 4 The widespread mechanistic approaches in biology
A common gene drive language eases regulatory process and eco-evolutionary extensions
18022P. Verma, R. G. Reeves and C. S. Gokhale, BMC Ecology and Evolution, 21:156. 2021-08-09 14:36:22.
Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The extraordinary diversity of plausible drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties, particularly where multiple approaches are combined. The sheer number of published manuscripts in this field, experimental and theoretical, the numerous techniques resulting in an explosion in the gene drive vocabulary hinder the regulators’ point of view. We address this concern by defining a simplified parameter based language of synthetic drives. Employing the classical population dynamics approach, we show that different drive construct (replacement) mechanisms can be condensed and evaluated on an equal footing even where they incorporate multiple replacement drives approaches. Using a common language, it is then possible to compare various model properties, a task desired by regulators and policymakers. The generalization allows us to extend the study of the invasion dynamics of replacement drives analytically and, in a spatial setting, the resilience of the released drive constructs. The derived framework is available as a standalone tool. Besides comparing available drive constructs, our tool is also useful for educational purpose. Users can also explore the evolutionary dynamics of future hypothetical combination drive scenarios. Thus, our results appraise the properties and robustness of drives and provide an intuitive and objective way for risk assessment, informing policies, and enhancing public engagement with proposed and future gene drive approaches.
Gene drives gaining speed
17972E. Bier, Nature Reviews Genetics, 2021-08-06 13:50:56.
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
The Promise of Genetics and Genomics for Improving Invasive Mammal Management on Islands
17936B. T. Burgess, R. L. Irvine, G. R. Howald and M. A. Russello, Frontiers in Ecology and Evolution, 9. 2021-08-03 13:21:15.
Invasive species are major contributors to global biodiversity decline. Invasive mammalian species (IMS), in particular, have profound negative effects in island systems that contain disproportionally high levels of species richness and endemism. The eradication and control of IMS have become important conservation tools for managing species invasions on islands, yet these management operations are often subject to failure due to knowledge gaps surrounding species- and system-specific characteristics, including invasion pathways and contemporary migration patterns. Here, we synthesize the literature on ways in which genetic and genomic tools have effectively informed IMS management on islands, specifically associated with the development and modification of biosecurity protocols, and the design and implementation of eradication and control programs. In spite of their demonstrated utility, we then explore the challenges that are preventing genetics and genomics from being implemented more frequently in IMS management operations from both academic and non-academic perspectives, and suggest possible solutions for breaking down these barriers. Finally, we discuss the potential application of genome editing to the future management of invasive species on islands, including the current state of the field and why islands may be effective targets for this emerging technology.
Invasive Mice and Engineered Genes
17952W. M. Adams and K. H. Redford, Yale University Press Blog, 2021-08-02 12:36:13.
On Gough Island, a steep speck of land deep in the South Atlantic, giant mice eat albatross chicks as they sit on their nests. They are house mice, accidental arrivals on the ships of long-dead sealers. But they have lost their secretive, timid, mousy ways. Over numerous generations, on an island without predators, they have become predators themselves. They have grown bigger, and fierce. The internet offers gruesome videos of Tristan albatross chicks being eaten alive in the night. The house mice of Gough Island are examples of one of the most serious and intractable drivers of biodiversity decline, invasive species. Not all species introduced by people outside their normal range become invasive, but invasive species are the most common threat to amphibians, reptiles, and mammals on the IUCN Red List, and have been a contributing cause in a quarter of plant extinctions and a third of animal extinctions in recent centuries. Traditional tools for addressing invasive species include traps, guns, fences, and particularly poisons. Though often effective, these often have undesired, and sometimes unexpected, knock-on effects on native species. Synthetic biology, the application of new genetic tools like CRISPR, is being explored as a source of new approaches to control with fewer side effects. The use of such methods in conservation blurs the distinction between what is natural and what is human-made.
2021 WHO guidelines on genetically modified mosquitoes
18084M. Makoni, The Lancet Microbe, 2:e353. 2021-08-01 17:27:59.
On May 19, 2021, WHO updated its guidelines for research and development on genetically modified mosquitoes, which define the standards for decision-making about how and when testing should proceed and describe best practices to ensure that research done in a public health context is safe, ethical, and rigorous. TDR, WHO's Special Programme for Research and Training in Tropical Diseases, and the GeneConvene Global Collaborative, an initiative of the Foundation for the National Institutes of Health, developed the updated guidelines building on the 2014 recommendations, integrating the latest advancements in mosquito genetic modification. “Vector-borne diseases are a major global public health issue. Over 100 countries are endemic for diseases such as dengue, malaria, and Zika. Dengue alone puts 2·5 billion people at risk”, says John Reeder (TDR and Department of Research for Health, WHO). Attacking the mosquitoes is an effective way of controlling the transmission of these diseases, but it is a massive task. “We are badly in need of new technologies that will change the game and allow effective, widespread control”, Reeder told The Lancet Microbe.
Scientists eradicate malaria-transmitting mosquitos using genetic engineering which make females infertile in new study which takes one step closer to wiping out the disease worldwide.
18078C. Ciaccia, Daily Mail, 2021-07-30 17:09:51.
Malaria kills nearly 500,000 people globally every year, but scientists have now figured out a way to use CRISPR gene-editing technology to make female mosquitoes infertile, described as a 'game-changer' for ending the deadly disease. Researchers from Imperial College London, Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine were able to use a gene drive for the first time to not only show that blocking female reproduction worked in a lab setting, but natural-like setting as well. The researchers targeted the mosquito species Anopheles gambiae, which is responsible for the majority of malaria transmissions in sub-Saharan Africa. The gene-drives targets the gene known as 'doublesex' in these mosquitoes.
Breakthrough in non-GMO malaria control
17914C. Robinson and J. Matthews, GM Watch, 2021-07-29 15:27:47.
A just-published study carried out in a high-security lab claims to show that a CRISPR gene drive (a way of forcing a heritable genetic modification through a whole species or population) can crash populations of malaria-spreading mosquitoes. But why crash mosquito populations with a risky experimental technology if you can completely stop them spreading malaria naturally? A naturally occurring biocontrol agent – a microbe – that inhibits the development of the malaria parasite in the mosquito Anopheles arabiensis, which spreads malaria in Sub-Saharan Africa, has recently been reported in the journal Nature Communications. Among the notable features of this approach are: • The microbe doesn’t seem to harm the mosquitoes in any way • Because it doesn’t kill the mosquitoes or cut their numbers, it should not have an impact on ecosystems dependent on them for food • The microbe seems to give the mosquitoes lifelong protection from malaria infection. The researchers are based at the International Centre of Insect Physiology and Ecology (ICIPE), Kenya, and in the UK. The microbe featured in their recent publication is a microsporidian. Microsporidia are unicellular spore-forming parasites that are now recognised as fungi, or as being related to fungi. All major animal groups harbour them, particularly insects. They spread horizontally, via spores that are ingested by a new host, but many also undergo vertical transmission to the next generation, via infected eggs (known as transovarial transmission).
Genetic engineering may rid world of malaria-transmitting mosquitoes
18163Y. Steinbuch, New York Post, 2021-07-29 14:35:51.
Scientists have eradicated a population of malaria-transmitting mosquitoes by using genetic engineering to make the females infertile — in what the lead researcher called a possible “game-changer in bringing about malaria elimination.” A team of researchers — led by scientists at Imperial College London, Italy’s Polo Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine — used the “gene drive” technology for the study, which was published in Nature Communications. “Gene drive is a self-sustaining and fast-acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines — and could be a game-changer in bringing about malaria elimination,” Andrew Hammond, a molecular biologist at Imperial College London, told the Guardian. Using the technology, scientists may circumvent natural selection by providing genetic instructions that will spread through a mosquito population and pass on a particular trait — in this case, infertility — much faster than could be attained through regular selective breeding, the outlet said.
Malaria-carrying mosquitoes could be bred out of existence using ‘gene drive’ technology
17923A. Wilkins, METRO, 2021-07-28 17:49:56.
Malaria-carrying mosquitoes have been eliminated using ‘gene drive’ technology in a nature-like environment, in a world-first study. By altering a gene that blocks female mosquito reproduction, and allowing that gene to spread, researchers found they could ensure complete mosquito population collapse within one year of the experiment’s start. It’s the first time so-called ‘gene drive’ technology has been shown to be effective in challenging ecological conditions over a long time scale. The results of the study, published in Nature Communications today, could be a key tool in battling the hundreds of millions of cases of malaria infections that happen each year. ‘The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa,’ said co-lead author of the study Dr. Drew Hammond. ‘Sadly, researchers estimate that Covid-19 related disruptions may have doubled mortality from malaria in 2020, threatening a setback of several decades. ‘Gene drive is a self-sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines – and could be a game-changer in bringing about malaria elimination.’
Scientists reveal controversial genetically modified mosquitoes in high-security lab
17920The Frontier Post, The Frontier Post, 2021-07-28 17:44:04.
Many years of additional research will be needed to prove the approach works and the mosquitoes would be safe to release into the wild. The project would also require regulatory approval and agreement by local residents in areas where those mosquitoes live, mostly in sub-Saharan Africa and parts of Asia. Despite years of efforts, malaria remains a major health problem. The mosquito-borne parasitic disease sickens more than 200 million people every year and kills more than 400,000, many of whom are children. So Muller and her colleagues decided to use CRISPR, a technique that enables scientists to easily make very precise changes in DNA to genetically modify the Anopheles gambiae species of mosquito, which spreads malaria in sub-Saharan Africa. The modification consisted of a mutation in a gene known as “doublesex,” which female mosquitoes need for normal development. The mutation deforms their mouths, making them unable to bite and spread the parasite. It also deforms their reproductive organs, rendering them unable to lay eggs. The mutation is combined with a gene drive, “effectively a selfish type of genetic element that spreads itself in the mosquito population,” says Tony Nolan of the Liverpool School of Tropical
Genetic engineering test with mosquitoes ‘may be game changer’ in eliminating malaria
17918L. Geddes, The Guardian, 2021-07-28 17:38:58.
Scientists have successfully wiped out a population of malaria-transmitting mosquitoes by using a radical form of genetic engineering to render the females infertile – in the most advanced and largest ever test of use of the technology to fight the disease. As well as bringing fresh hope in the fight against one of the world’s biggest killers, the study lays the foundations for further trials of gene-drive technology, which could mean self-destroying mosquitoes being released into the wild within 10 years. “This is a very exciting development,” said Dr Thomas Price, a senior lecturer in evolution, ecology and behaviour at the University of Liverpool, who was not involved in the research. “There are still lots of ethical and regulatory questions that need answering. But none of those really matter if it is impossible to build gene drives that are effective in the field. This is a major step towards achieving that.” Despite the reduction in malaria over recent decades there were still 229m cases of the disease in 2019, and 409,000 deaths. Dr Drew Hammond, at Imperial College London, who led the new research, said: “Gene drive is a self sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines, and could be a game changer in bringing about malaria elimination.”
World Nature Conservation Day: Technology to Forge a Path for Nature Conservation and Communities
17912P. Becker, Isand Conservation, 2021-07-28 15:23:24.
Gene drives are a genetic phenomenon that occurs in nature and causes a gene or trait to have a greater than 50% chance of inheritance. Island Conservation and partners have formed the Genetic Biocontrol of Invasive Rodents (GBIRd) partnership, to explore the technical and social feasibility of creating a gene drive to eliminate invasive rodents on islands. For example, a gene drive that causes rats to produce all male offspring spreads through an invasive population until there is no natural recruitment. On this World Nature Conservation Day, I would like to invite you to reflect on the scale, speed and costs of the efforts needed to address current conservation challenges. Gene drive could be a game-changer for conservation, making nature restoration and sustainable development gains possible on islands where these are currently out of reach today. Combined with existing tools, gene drive could transform the future of island restoration, drastically increasing the scope, scale, and pace of our work, and realizing benefits for island wildlife and communities around the world.
How An Altered Strand Of DNA Can Cause Malaria-Spreading Mosquitoes To Self-Destruct
17862R. Stein, NPR, 2021-07-28 15:19:15.
For the first time, scientists have shown that a new kind of genetic engineering can crash populations of malaria-spreading mosquitoes. In the landmark study, published Wednesday in the journal Nature Communications, researchers placed the genetically modified mosquitoes in a special laboratory that simulated the conditions in sub-Saharan Africa, where they spread the deadly disease. The male mosquitoes were engineered with a sequence of DNA known as a "gene drive" that can rapidly transmit a deleterious mutation that essentially wipes out populations of the insects. The goal is to create a powerful new tool to fight malaria, which remains one of the world's most terrible scourges. "Our study is the first [that] could show that gene-drive technology works under ecologically challenging conditions," says Ruth Muller, an entomologist who led the research at PoloGGB, a high-security lab in Terni, Italy. "This is the big breakthrough that we made with our study."
A lab experiment shows that we could engineer malaria-carrying mosquitoes to kill themselves off
17909A. Micu, ZME Science, 2021-07-28 15:17:37.
A new paper showcases how genetic engineering can be used to cause populations of malaria-spreading mosquitoes to self-destroy. An international research effort has shown, in the context of a lab experiment, that male mosquitoes engineered to carry a certain strand of DNA can rapidly destroy entire groups of these blood-sucking insects. The main importance of this experiment is that it showcases that gene-drive technology can be used even in harsh environmental conditions, such as those in sub-Saharan Africa. This “gene drive” sequence is essentially a damaging mutation that could prove to be a powerful tool against the carriers of malaria.
Malarial mosquitoes suppressed in experiments that mimic natural environments
17903H. Dunning, Phys Org, 2021-07-28 14:58:38.
Researchers have shown "gene drive" technology, which spreads a genetic modification blocking female reproduction, works in natural-like settings. The team, led by researchers from Imperial College London, Polo GGB and Liverpool School of Tropical Medicine were able to suppress populations of a malaria-carrying mosquito in a year-long experiment mimicking natural environments. This is the first time a gene drive has been shown to be as effective as expected when tested in challenging ecological conditions over a long timescale. The results are published today in Nature Communications. Despite the reduction in malaria over recent decades, there were still 229 million cases of malaria in 2019—an increase on the previous year—and 409,000 deaths. Co-lead author of the study Dr. Drew Hammond, from the Department of Life Sciences at Imperial College London and the Johns Hopkins Malaria Research Institute, said: "The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa.
Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field
17853A. Hammond, P. Pollegioni, T. Persampieri, A. North, R. Minuz, A. Trusso, A. Bucci, K. Kyrou, I. Morianou, A. Simoni, T. Nolan, R. Müller and A. Crisanti, Nature Communications, 12:4589. 2021-07-28 12:31:16.
CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings. Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.
Gene drive strategies of pest control in agricultural systems: challenges and opportunities
17836M. Legros, J. M. Marshall, S. Macfadyen, K. R. Hayes, A. Sheppard and L. G. Barrett, Evolutionary Applications, 2021-07-26 14:04:32.
Abstract Recent advances in gene editing technologies have opened new avenues for genetic pest control strategies, in particular around the use of gene drives to suppress or modify pest populations. Significant uncertainty, however, surrounds the applicability of these strategies to novel target species, their efficacy in natural populations, and their eventual safety and acceptability as control methods. In this article we identify issues associated with the potential use of gene drives in agricultural systems, to control pests and diseases that impose a significant cost to agriculture around the world. We first review the need for innovative approaches, and provide an overview of the most relevant biological and ecological traits of agricultural pests that could impact the outcome of gene drive approaches. We then describe the specific challenges associated with using gene drives in agricultural systems, as well as the opportunities that these environments may offer, focusing in particular on the advantages of high-threshold gene drives. Overall we aim to provide a comprehensive view of the potential opportunities and the remaining uncertainties around the use of gene drives in agricultural systems.
Resistance to a CRISPR-based gene drive at an evolutionarily conserved site is revealed by mimicking genotype fixation
17940S. Fuchs, W. Garrood, A. Beber, A. Hammond, R. Galizi, M. Gribble, G. Morselli, T.-Y. Hui, K. Willis, N. Kranjc, A. Burt, T. Nolan and A. Crisanti, bioRxiv, 2021-07-26 13:48:52.
CRISPR-based homing gene drives can be designed to disrupt essential genes whilst biasing their own inheritance, leading to suppression of mosquito populations in the laboratory. This class of gene drives relies on CRISPR-Cas9 cleavage of a target sequence and copying (‘homing’) therein of the gene drive element from the homologous chromosome. However, target site mutations that are resistant to cleavage yet maintain the function of the essential gene are expected to be strongly selected for. Targeting functionally constrained regions where mutations are not easily tolerated should lower the probability of resistance. Evolutionary conservation at the sequence level is often a reliable indicator of functional constraint, though the actual level of underlying constraint between one conserved sequence and another can vary widely. Here we generated a novel gene drive in the malaria vector Anopheles gambiae , targeting an ultra-conserved target site in a haplosufficient essential gene (AGAP029113) required during mosquito development, which fulfils many of the criteria for the target of a population suppression gene drive. We then designed a selection regime to experimentally assess the likelihood of generation and subsequent selection of gene drive resistant mutations at its target site. We simulated, in a caged population, a scenario where the gene drive was approaching fixation, where selection for resistance is expected to be strongest. Continuous sampling of the target locus revealed that a single, restorative, in-frame nucleotide substitution was selected. Our findings show that ultra-conservation alone need not be predictive of a site that is refractory to target site resistance. Our strategy to evaluate resistance in vivo could help to validate candidate gene drive targets for their resilience to resistance and help to improve predictions of the invasion dynamics of gene drives in field populations. <h4>Author summary</h4> Gene drives have the potential to be applied as novel control strategy of disease-transmitting mosquitoes, by spreading genetic traits that suppress or modify the target population. Many gene drive elements work by recognising and cutting a specific target sequence in the mosquito genome and copying themselves into that target sequence allowing the gene drive to increase in frequency in the population. Like other mosquito control interventions, efficacy will greatly depend on minimising the development of resistance to the gene drive mechanism - most likely via a change in the target sequence that prevents further cutting. One strategy to reduce resistance is to target sequences that are highly conserved, which implies that changes cannot easily be tolerated. We developed a strategy that simulates high selection pressure, under which resistance is most likely to emerge, and therefore provides a stringent test of its propensity to arise. Unlike previous results with another gene drive, we recovered a resistant allele within a few generations of gene drive exposure and at high frequency. Our results show that conserved sequences can vary hugely in ability to tolerate mutations and highlights the need to functionally validate future candidate gene drive target sites for their robustness to resistance.
Risk management recommendations for environmental releases of gene drive modified insects
17829Y. Devos, J. D. Mumford, M. B. Bonsall, D. C. M. Glandorf and H. D. Quemada, Biotechnology Advances, 2021-07-25 13:02:06.
The ability to engineer gene drives (genetic elements that bias their own inheritance) has sparked enthusiasm and concerns. Engineered gene drives could potentially be used to address long-standing challenges in the control of insect disease vectors, agricultural pests and invasive species, or help to rescue endangered species. However, risk concerns and uncertainty associated with potential environmental release of gene drive modified insects (GDMIs) have led some stakeholders to call for a global moratorium on such releases or the application of other strict precautionary measures to mitigate perceived risk assessment and risk management challenges. Instead, we provide recommendations that may help to improve the relevance of risk assessment and risk management frameworks for environmental releases of GDMIs. These recommendations include: (1) developing additional and more practical risk assessment guidance to ensure appropriate levels of safety; (2) making policy goals and regulatory decision-making criteria operational for use in risk assessment so that what constitutes harm is clearly defined; (3) ensuring a more dynamic interplay between risk assessment and risk management to manage uncertainty through closely interlinked pre-release modelling and post-release monitoring; (4) considering potential risks against potential benefits, and comparing them with those of alternative actions to account for a wider (management) context; and (5) implementing a modular, phased approach to authorisations for incremental acceptance and management of risks and uncertainty. Along with providing stakeholder engagement opportunities in the risk analysis process, the recommendations proposed may enable risk managers to make choices that are more proportionate and adaptive to potential risks, uncertainty and benefits of GDMI applications, and socially robust.
GM mosquitoes to fight malaria
17818I. Khisa, The INDEPENDENT, 2021-07-19 14:40:06.
Scientists at the Uganda Virus Research Institute (UVRI) plans to undertake a research on genetically engineered mosquitoes to tackle malaria. Dr. Jonathan Kayondo, the principal investigator Target Malaria Uganda and Senior Research Officer at UVRI had an email interview with The Independent’s Isaac Khisa about the research and here are the excerpts: n Uganda, Target Malaria’s research is still in early stages, currently at facility readiness. The Uganda Virus Research Institute became a primary Target Malaria project site in 2016. We have been laying the research groundwork by setting up the necessary infrastructure and building capacity of the teams. We constructed a new Arthropod Containment Level 2 (ACL2) insectary to facilitate future studies on development and evaluation of genetically modified mosquitoes following international containment guidelines and best practices. It was inaugurated in July 2019. Our teams are currently testing the facility for functionality by studying the local wild mosquitoes under containment and developing standard operating procedures (SOPs) as part of the capacity building efforts. We are also busy developing stakeholder engagement strategies and preparing to apply for regulatory approval for the next stage of our research.
Combating mosquito-borne diseases using genetic control technologies
17735G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari, Nature Communications, 12:4388. 2021-07-19 13:06:45.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito control strategies including gene drives have been developed to address these problems, both requiring the release of modified mosquitoes into the environment. Here, we review the latest developments, notable similarities, and critical distinctions between these promising technologies and discuss their future applications for mosquito-borne disease control.
Genetically Modifying Bats Could Prevent the Next Pandemic, Scientists Say
17744G. Dutton, BioSpace, 2021-07-15 13:26:12.
The next COVID pandemic could be prevented by using a gene drive to preemptively edit the genome of bats to prevent them from becoming hosts for coronaviruses, according to a proposal by scientists from Israel’s Interdisciplinary Center (IDC) Herzelia and the National Institutes of Health (NIH). Meanwhile, a team of researchers from Imperial College London is devising a way to prevent gene drives from spreading and conferring heritable, anti-competitive traits to entire populations. The two projects may be in conflict with one another, or the London project may provide a degree of safety that could manage unintended consequences. The IDC/NIH plan, Preventing COVID-59, was published recently on GitHub by Uaniv Erlich of the (IDC) and Daniel Douek of the Vaccine Research Center, National Institute of Allergies and Infectious Diseases at the NIH in the U.S. Its premise is that the SARS-CoV-2 virus – the third such virus to infect humans in the past 20 years – is part of a growing pattern of betacoronaviruses infecting human populations.
Gene Drives – Engineering the Wild
17825L. Sharratt, Sentinel, 2021-07-13 14:52:05.
So far, genetically engineered organisms have been mostly limited to agricultural use, with partial success. Around the world, a few major crops (mostly corn, soy, and cotton) are genetically engineered, predominantly for herbicide tolerance and insect resistance. However, the newer techniques of genome editing (also called gene editing) mean that a much wider variety of organisms can now be genetically engineered, including for many purposes outside of food and farming. This increased power is most dramatically illustrated in the development of gene drive technology. Unlike genetically engineered plants and animals intended for confined use in agricultural production, gene drive organisms are expressly designed for intentional, long-lived release into the wild. Gene drives are a technology through which a few individual genetically engineered organisms would be deployed to intentionally push new genes through an entire population of a species in the wild or in a farm ecosystem. Through the gene drive mechanism, new genes would be inherited by all offspring in subsequent generations, not just the expected half in normal inheritance. When gene drive organisms reproduce, specific traits as well as the gene drive mechanism itself would be passed on. Making such spreading genetic changes to an organism, or eliminating it in the wild, could disrupt whole ecosystems in ways that are difficult or impossible to predict or reverse.
Mice Plague Eastern Australia in Record Numbers
17751B. Nogrady, The Scientist, 2021-07-12 13:50:17.
Just before Christmas last year, Julie Leven and her husband Des took their camper up to visit their son in northern New South Wales, Australia. Driving back at night to their home in Gilgandra, around 430 kilometers northwest of Sydney, they saw masses of white spots moving across the dark road surface. The spots, they soon realized, were mice. Once they reached their house, the Levens saw a scene of rodent devastation. Mice had invaded their home in such numbers that it was unlivable. The creatures had gnawed their way into the pantry and ruined all the food they could get into. Their droppings and pungent urine were spread from one end of the dwelling to the other, across soft furnishings and bedding. The rodents had even eaten the insulation around the engine wiring in two tractors and ruined their harvested hay bales.
Autocatalytic-protection for an unknown locus CRISPR-Cas countermeasure for undesired mutagenic chain reactions
17969E. Schonfeld, E. Schonfeld and D. Schonfeld, Journal of Theoretical Biology, 528:110831. 2021-07-11 13:41:33.
The mutagenic chain reaction (MCR) is a genetic tool to use a CRISPR–Cas construct to introduce a homing endonuclease, allowing gene drive to influence whole populations in a minimal number of generations (Esvelt et al., 2014, Gantz and Bier, 2015, Gantz and Bier, 2016). The question arises: if an active genetic terror event is released into a population, could we prevent the total spread of the undesired allele (Gantz, et al., 2015, Webber et al., 2015)? Thus far, effective protection methods require knowledge of the terror locus (Grunwald et al., 2019). Here we introduce a novel approach, an autocatalytic-Protection for an Unknown Locus (a-PUL), whose aim is to spread through a population and arrest and decrease an active terror event’s spread without any prior knowledge of the terror-modified locus, thus allowing later natural selection and ERACR drives to restore the normal locus (Hammond et al., 2017). a-PUL, using a mutagenic chain reaction, includes (i) a segment encoding a non-Cas9 endonuclease capable of homology-directed repair suggested as Type II endonuclease Cpf1 (Cas12a), (ii) a ubiquitously-expressed gene encoding a gRNA (gRNA1) with a U4AU4 3′-overhang specific to Cpf1 and with crRNA specific to some desired genomic sequence of non-coding DNA, (iii) a ubiquitously-expressed gene encoding two gRNAs (gRNA2/gRNA3) both with tracrRNA specific to Cas9 and crRNA specific to two distinct sites of the Cas9 locus, and (iv) homology arms flanking the Cpf1/gRNA1/gRNA2/gRNA3 cassette that are identical to the region surrounding the target cut directed by gRNA1 (Khan, 2016, Zetsche et al., 2015). We demonstrate the proof-of-concept and efficacy of our protection construct through a Graphical Markov model and computer simulation.
Part of ‘master plan’: Researchers receive grant to fund research on malaria
17748L. Huang, The Daily Californian, 2021-07-11 13:33:25.
Early this month, The Marshall Lab at UC Berkeley received an $800,000 grant from the Bill and Melinda Gates Foundation to fund its research on genetics-based malaria mosquito control. The Marshall Lab is one of many teams playing a part in the Gates Foundation’s decades-long “master plan” to eradicate malaria, according to associate professor John Marshall, the project’s principal investigator. Based on data from the World Health Organization, malaria kills hundreds of thousands of people a year. The lab has focused on malaria prevention ever since it opened its doors in 2015, publishing work about mosquito intervention and control mechanisms related to genetic mathematical modeling. “If you have a drug to control malaria or a mosquito net, then how that is implemented on a continental scale is more than a problem of having the intervention itself — you need to think about the numbers involved,” Marshall said. Marshall compared mosquitoes to humans in that they have similar genetic makeups. He said some mosquito genes can be altered to either prevent disease transmission to humans or reduce rates of mosquito reproduction. Marshall’s team plans to apply its Mosquito Gene Drive Explorer, which simulates releases of genetically modified mosquitoes into habitats, to aid fellow researchers funded by the Gates Foundation. With the system, researchers can identify the efficacy of systems for reducing cases of malaria in order to pinpoint which characteristics of gene constructs can be prioritized to most efficiently suppress the disease.
Africa Turning to Gene Drive Technology for Malaria Elimination
17669M. Hearty, Science Africa, 2021-07-09 20:02:22.
With Africa accounting for nine out of ten malaria cases globally, the continent is turning to gene drive technology to control the disease. This is according to a decision made by African leaders at the 29th Summit of Heads of States and Governments of the African Union held in Addis Ababa. There are 3500 to 4000 mosquito species worldwide and 837 of the species are in Africa, with only 3 species transmitting malaria in sub-Saharan Africa. Speaking during a virtual conference by the African Union Development Agency (AUDA-NEPAD) , Dr Abdoulaye Diabate, Head of Medical Entomology and Parasitology at the Research Institute in health Sciences in Burkina Faso who presented on Gene Drive for Malaria Control and Elimination in Africa said that two options for genetic control of mosquito-borne infectious diseases identified were population suppression and population replacement. “Population suppression involves releasing of modified mosquitoes into the population, and this can cause transient or permanent suppression. With the population replacement method, modified mosquitoes released into the population can lead to the spread of a gene that blocks malaria transmission,” the Medical Entomologist stated.
A new tool in the global fight against malaria
17666S. Laux, Brighter World, 2021-07-08 19:56:20.
McMaster researchers with the Institute on Ethics & Policy for Innovation (IEPI) have played a key role in developing updated international guidelines that will inform research and development on genetically modified mosquitoes – an initiative that could significantly affect global efforts to eradicate mosquito-borne illnesses such as dengue fever, Zika virus and malaria. Released by the World Health Organization in late May, the guidelines describe best practices to ensure that the study of genetically modified mosquitoes is scientifically rigorous and meets essential standards of safety, effectiveness, accessibility and ethics. “The previous World Health Organization guidance for testing genetically modified mosquitoes was from 2014 – and since then, there have been multiple technological developments and considerable scientific progress,” explains Claudia Emerson, the director of IEPI and a professor of philosophy who, along with IEPI researchers Travis Ramsay and Aaron Roberts, developed the guidance’s chapter on ethical considerations. “Genetically modifying organisms isn’t new, at least not from an ethical or scientific perspective – but as the technology has developed over the years, especially with respect to mosquitoes, there has been a change in its perception and the receptivity to using it. It was important to update the guidance to reflect these changes.”
West African countries working together to develop framework to regulate genetically engineered mosquitos: Target Malaria
17663Anonymous, Global News, 2021-07-08 19:50:08.
Abdoulaye Diabaté, principal investigator for Target Malaria, says West African countries like Burkina Faso, Mali and Benin are working with the New Partnership for Africa’s Development (NEPAD) to develop a pan-West African framework to regulate gene drive mosquitos.
Marshall Lab receives Gates grant for genetics-based malaria mosquito control
17654Berkeley Public Health, Berkeley Public Health, 2021-07-08 19:33:19.
Berkeley Public Health Associate Professor John Marshall, PhD, and Assistant Project Scientist Héctor Sánchez, PhD, have received an $800,000 grant from the Bill & Melinda Gates Foundation to support their lab’s work in genetics-based malaria mosquito control. Malaria, the most devastating mosquito-borne disease, poses a major public health burden throughout much of the world. Novel genetics-based tools that can be shown to be safe and effective would be transformative in eliminating the disease and the suffering it causes. “Malaria continues to be exceptionally difficult to eliminate with currently-available tools,” said Marshall. “Insecticide-treated nets and antimalarial drugs have succeeded in reducing the African malaria burden by about a half, but their impact has stagnated in recent years and new tools are needed. There is now growing recognition that the most promising new tools for malaria elimination are vaccines and gene-edited mosquitoes.”
Scientists develop new technology that gives greater control for managing malaria mosquitoes
17650Keele University, Phy Org, 2021-07-06 19:19:27.
Researchers including a Keele University scientist have engineered an innovative approach to disable highly powerful genetic devices that control harmful insect populations. Dr. Roberto Galizi from Keele's School of Life Sciences was part of a research team that previously developed gene drive technologies that proved highly effective in eliminating populations of mosquitoes in the laboratory, offering a powerful new strategy to prevent deadly vector-borne disease such as malaria. Gene drive elements inserted in the mosquito genome can rapidly spread genetic modifications, such as impairment of fertility, throughout the entire population target by biasing their genetic inheritance after mating with wild insects. The gene drive technologies show great potential for suppressing the mosquito species that transmit malaria with increased power compared to other methods, thanks to their capacity to self-spread through the population. However, this also makes it difficult to retain control of this technology once released. So to combat this, the researchers have now developed an innovative and highly effective technology that allows them to control and even reverse the effects of gene drives.
Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in Drosophila
17609G. Oberhofer, B. Hay and T. Ivy, bioRxiv, 2021.07.03.451005. 2021-07-04 14:38:01.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and gRNAs to disrupt endogenous versions of an essential gene, while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. In consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition-dependent, so too will be the survival of that population. To test this idea we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23° C, but when populations now dependent on TS-ClvRdbe are shifted to 29° C death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in HEG-based drive, and to bring about suppression and/or killing of specific individuals in response to other stimuli.Competing Interest StatementThe authors have filed patent applications on ClvR and related 336 technologies (U.S. Application No. 15/970,728 and No. 16/673,823 ; provisional patent No. 337 CIT-8511-P )
Gene Drive: The Technology and its Potentials for Biodiversity Conservatio
17611Z. Bugnosen, Science Speaks, 2021-07-01 14:43:19.
Gene drive is a gene editing tool that is rapidly advancing as scientists investigate further its potentials to address concerns related to agriculture, the environment, and even human health. To help the public understand it better, ISAAA and its network of Biotechnology Information Centers, in partnership with the Outreach Network for Gene Drive Research, launched the four-part Gene Drive Webinar Series. Gene drive experts were invited to talk about the technology and how it can help conserve biodiversity during the first two sessions of the series.
Could editing the genomes of bats prevent future coronavirus pandemics? Two scientists think it’s worth a try
17602E. C. Hayden, STAT, 2021-07-01 14:21:06.
Amid the devastating Covid-19 pandemic, two researchers are proposing a drastic way to stop future pandemics: using a technology called a gene drive to rewrite the DNA of bats to prevent them from becoming infected with coronaviruses. The scientists aim to block spillover events, in which viruses jump from infected bats to humans — one suspected source of the coronavirus that causes Covid. Spillover events are thought to have sparked other coronavirus outbreaks as well, including SARS-1 in the early 2000s and Middle East respiratory syndrome (MERS). This appears to be the first time that scientists have proposed using the still-nascent gene drive technology to stop outbreaks by rendering bats immune to coronaviruses, though other teams are investigating its use to stop mosquitoes and mice from spreading malaria and
Preventing COVID-59
17604Y. Erlich and D. Douek, github, 2021-06-30 14:30:52.
SARS-CoV-2 is the third betacoronavirus to enter the human population in the past 20 years, revealing a concerning pattern. Clearly, preventing a future pandemic from such viruses is a critical priority. Previous studies have shown that shRNAs can be powerful suppressors of RNA viruses in transgenic animals and substantially reduce transmission. Thus, we propose the introduction of anti-betacoronavirus shRNAs using CRISPR/CAS9 gene drive into the horseshoe bat population, the natural reservoir of those viruses, to combat this pandemic threat at its source. Importantly, our approach is not expected to create any harm to bats and can benefit other animals in the ecosystem that contract betacoronaviruses from bats. We map the ethical and the technical aspects and suggest guidelines for moving forward with this proposal.
INSIDER: alignment-free detection of foreign DNA sequences
17657A. P. Tay, B. Hosking, C. Hosking, D. C. Bauer and L. O. W. Wilson, Computational and Structural Biotechnology Journal, 19:3810-3816. 2021-06-29 19:39:26.
External DNA sequences can be inserted into an organism’s genome either through natural processes such as gene transfer, or through targeted genome engineering strategies. Being able to robustly identify such foreign DNA is a crucial capability for health and biosecurity applications, such as anti-microbial resistance (AMR) detection or monitoring gene drives. This capability does not exist for poorly characterised host genomes or with limited information about the integrated sequence. To address this, we developed the INserted Sequence Information DEtectoR (INSIDER). INSIDER analyses whole genome sequencing data and identifies segments of potentially foreign origin by their significant shift in k-mer signatures. We demonstrate the power of INSIDER to separate integrated DNA sequences from normal genomic sequences on a synthetic dataset simulating the insertion of a CRISPR-Cas gene drive into wild-type yeast. As a proof-of-concept, we use INSIDER to detect the exact AMR plasmid in whole genome sequencing data from a Citrobacter freundii patient isolate. INSIDER streamlines the process of identifying integrated DNA in poorly characterised wild species or when the insert is of unknown origin, thus enhancing the monitoring of emerging biosecurity threats.
The (Losing) Battle Against Mosquitoes In Texas
17599J. Clayton, Texas Public Radio, 2021-06-26 14:13:20.
Jerry Clayton: Mosquitoes are a fact of life in Texas, and the battle against the pesky biting insects is never ending. But there are some new weapons on the horizon. Zach Adleman is an associate professor of entomology at Texas A&M University. He joins us today. Thanks for being here, Zach.
A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression
17565C. Taxiarchi, A. Beaghton, N. I. Don, K. Kyrou, M. Gribble, D. Shittu, S. P. Collins, C. L. Beisel, R. Galizi and A. Crisanti, Nature Communications, 12:3977. 2021-06-25 15:00:05.
CRISPR-based gene drives offer promising means to reduce the burden of pests and vector-borne diseases. These techniques consist of releasing genetically modified organisms carrying CRISPR-Cas nucleases designed to bias their inheritance and rapidly propagate desired modifications. Gene drives can be intended to reduce reproductive capacity of harmful insects or spread anti-pathogen effectors through wild populations, even when these confer fitness disadvantages. Technologies capable of halting the spread of gene drives may prove highly valuable in controlling, counteracting, and even reverting their effect on individual organisms as well as entire populations. Here we show engineering and testing of a genetic approach, based on the germline expression of a phage-derived anti-CRISPR protein (AcrIIA4), able to inactivate CRISPR-based gene drives and restore their inheritance to Mendelian rates in the malaria vector Anopheles gambiae. Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes.
UC San Diego scientists develop the first CRISPR/Cas9-based gene drive in plants
17563M. Aguilera, UC San Diego News Center, 2021-06-25 14:55:55.
With a goal of breeding resilient crops that are better able to withstand drought and disease, University of California San Diego scientists have developed the first CRISPR-Cas9-based gene drive in plants. While gene drive technology has been developed in insects to help stop the spread of vector-borne diseases such as malaria, researchers in Professor Yunde Zhao's lab, along with colleagues at the Salk Institute for Biological Studies, demonstrated the successful design of a CRISPR-Cas9-based gene drive that cuts and copies genetic elements in Arabidopsis plants. Breaking from the traditional inheritance rules that dictate that offspring acquire genetic materials equally from each parent (Mendelian genetics), the new research uses CRISPR-Cas9 editing to transmit specific, targeted traits from a single parent in subsequent generations. Such genetic engineering could be used in agriculture to help plants defend against diseases to grow more productive crops. The technology also could help fortify plants against the impacts of climate change such as increased drought conditions in a warming world.
Using gene drives to control malaria
17594A. Fell, Daily News, 2021-06-25 14:08:33.
A group of UC scientists led by Greg Lanzaro, professor of pathology, microbiology and immunology in the UC Davis School of Veterinary Medicine, recently completed an analysis of a strategy aimed at eliminating malaria from Africa using genetically engineered mosquitoes. Lanzaro’s lab is part of the UC Irvine Malaria Initiative. The laboratories of Anthony James at UC Irvine and Ethan Bier at UC San Diego engineered mosquitoes with synthetic genes that render them incapable of transmitting the malaria parasite and coupled these genes with a CRISPR-Cas9 gene drive to promote their spread into malaria vector populations in Africa. The idea is to ‘drive’ the new malaria-resistance genes into the mosquito population at a much higher rate than could occur naturally.
Potential use of gene drive modified insects against disease vectors, agricultural pests and invasive species poses new challenges for risk assessment
17551Y. Devos, J. D. Mumford, M. B. Bonsall, A. M. Camargo, L. G. Firbank, D. C. M. Glandorf, F. Nogué, K. Paraskevopoulos and E. A. Wimmer, Critical Reviews in Biotechnology, 2021-06-24 13:49:18.
Potential future application of engineered gene drives (GDs), which bias their own inheritance and can spread genetic modifications in wild target populations, has sparked both enthusiasm and concern. Engineered GDs in insects could potentially be used to address long-standing challenges in control of disease vectors, agricultural pests and invasive species, or help to rescue endangered species, and thus provide important public benefits. However, there are concerns that the deliberate environmental release of GD modified insects may pose different or new harms to animal and human health and the wider environment, and raise novel challenges for risk assessment. Risk assessors, risk managers, developers, potential applicants and other stakeholders at many levels are currently discussing whether there is a need to develop new or additional risk assessment guidance for the environmental release of GD modified organisms, including insects. Developing new or additional guidance that is useful and practical is a challenge, especially at an international level, as risk assessors, risk managers and many other stakeholders have different, often contrasting, opinions and perspectives toward the environmental release of GD modified organisms, and on the adequacy of current risk assessment frameworks for such organisms. Here, we offer recommendations to overcome some of the challenges associated with the potential future development of new or additional risk assessment guidance for GD modified insects and provide considerations on areas where further risk assessment guidance may be required.
Selective inheritance of target genes from only one parent of sexually reproduced F1 progeny in Arabidopsis
17567T. Zhang, M. Mudgett, R. Rambabu, B. Abramson, X. Dai, T. P. Michael and Y. Zhao, Nature Communications, 12:3854. 2021-06-22 15:05:16.
Sexual reproduction constrains progeny to inherit allelic genes from both parents. Selective acquisition of target genes from only one parent in the F1 generation of plants has many potential applications including the elimination of undesired alleles and acceleration of trait stacking. CRISPR/Cas9-based gene drives can generate biased transmission of a preferred allele and convert heterozygotes to homozygotes in insects and mice, but similar strategies have not been implementable in plants because of a lack of efficient homology-directed repair (HDR). Here, we place a gene drive, which consists of cassettes that produce Cas9, guide RNAs (gRNA), and fluorescent markers, into the CRYPTOCHROME 1 (CRY1) gene through CRISPR/Cas9-mediated HDR, resulting in cry1drive lines. After crossing the cry1drive/cry1drive lines to wild type, we observe F1 plants which have DNA at the CRY1 locus from only the cry1drive/cry1drive parent. Moreover, a non-autonomous trans-acting gene drive, in which the gene drive unit and the target gene are located on different chromosomes, converts a heterozygous mutation in the target gene to homozygous. Our results demonstrate that homozygous F1 plants can be obtained through zygotic conversion using a CRISPR/Cas9-based gene drive.
Sustainable Food Production: The Contribution of Genome Editing in Livestock
17590A. Menchaca, Sustainability, 13. 2021-06-21 13:52:55.
This article is focused on the scope and perspectives for the application of this technology, which includes improving production traits, enhancing animal welfare through adaptation and resilience, conferring resistance to infectious diseases, and suppressing pests and invasive species that threaten livestock. The main advantages and concerns that should be overcome by science, policy and people are discussed with the aim that this technology can make a real contribution to our collective future. This review is part of the special issue “Genome Editing in Animal Systems to Support Sustainable Farming and Pest Control”.
Population modification strategies for malaria vector control are uniquely resilient to observed levels of gene drive resistance alleles
17502G. C. Lanzaro, H. M. Sánchez C, T. C. Collier, J. M. Marshall and A. A. James, BioEssays, 2021-06-20 13:46:45.
Cas9/guide RNA (gRNA)-based gene drive systems are expected to play a transformative role in malaria elimination efforts., whether through population modification, in which the drive system contains parasite-refractory genes, or population suppression, in which the drive system induces a severe fitness load resulting in population decline or extinction. DNA sequence polymorphisms representing alternate alleles at gRNA target sites may confer a drive-resistant phenotype in individuals carrying them. Modeling predicts that, for observed levels of SGV at potential target sites and observed rates of de novo DRA formation, population modification strategies are uniquely resilient to DRAs. We conclude that gene drives can succeed when fitness costs incurred by drive-carrying mosquitoes are low enough to prevent strong positive selection for DRAs produced de novo or as part of the SGV and that population modification strategies are less prone to failure due to drive resistance.
Selfish DNA: how new gene technology could stop the advance of mice
17450M. McMillan, Tentenfield Star, 2021-06-15 17:20:08.
It used to be that seeing a mouse in the house was a rare occurrence. Now, it's rarely a day that goes by where we aren't seeing or hearing the little vermin. Current methods of baiting and trapping are struggling to control the plague of mice spreading across regional Australia. But a $1.8 million investment from the NSW government might soon give us a new weapon in the war. The government is investing in research into the use of gene drives, or "selfish DNA" - a genetic tool that can help us to control pests. How? Well, to understand gene drives we first need to understand the normal way in which genes are inherited. Mice, like humans, have two copies of each gene, one inherited from their mother and one from their father. We call these copies alleles, and they can be exactly the same or slightly different from each other. Normally, there is a 50/50 chance as to which allele will be passed on to any offspring. If one allele carries some sort of mutation, there is a 50 per cent chance that it will be passed on.
‘Nigeria has capacity for safe application of modern biotechnology’
17298M. Adewale, The Guardian, 2021-06-09 11:00:41.
Director-general of the National Biosafety Management Agency (NBMA), Dr. Rufus Ebegba, has declared that Nigeria has the capacity to deploy safe biotechnology products for agricultural development and environmental safety. Ebegba, who gave the assurance at the opening of a two-day retreat on agricultural biotechnology for media practitioners and extension workers yesterday in Kano, explained that Nigeria possessed the institutional capacity and policy framework to ensure the application of modern technology, especially on agricultural production with the potential to accelerate food security and reduce import dependency. He stressed that the establishment of the NBDA, which necessitated the development of national policy on biotechnology in 2001 and the enactment of the agency, mandated to ensure the safety of modern biotechnology products, has positioned the country with the knowledge to deploy Genetically Modified Organisms (GMOs) products. Ebegba stressed that part of the core responsibility of NBDA was to ensure the regulation of biotechnology and the safety of GMO products for human health and the environment.
European Parliament calls for ban on gene drive technology
17296Save Our Seeds, Save Our Seeds, 2021-06-09 10:56:17.
The European Parliament yesterday confirmedi it‘s precautionary stance towards the use of a new genetic engineering technology called gene drive. In its report on the EU’s Biodiversity Strategy for 2030, adopted at the European Parliament’s plenary on 08.06.2021, Parliamentarians demand that „no releases of genetically engineered gene drive organisms should be allowed, including for nature conservation purposes, in line with the precautionary principle.“ Mareike Imken, coordinator of the European Stop Gene Drive Campaign welcomes this decision and comments: „With its position today, the European Parliament recognizes that this technology raises a series of scientific, regulatory, societal and ethical questions and concerns. As its use could severely harm biodiversity, the European Parliament calls to postpone any environmental releases until these questions have been addressed and settled. This is an important message that should feed into the ongoing discussions about global regulations at the next meeting of the International Union for Conservation of Nature (IUCN) in September in Marseille and those of the Convention on Biological Diversity in October in Kunming, China.“ 27 civil society and science organisations from across the EU had sent a letter to Parliamentarians in support of the amendment ahead of the vote. It „provides reasonable suggestions on how to implement the European Parliament’s previous position in its resolution on the 15th meeting of the Conference of Parties (COP15) to the Convention on Biological Diversity (2019/2824(RSP)“. In that previous position, adopted in January 2020, the European Parliament had called “on the Commission and the Member States to call for a global moratorium at the COP15 on releases of gene drive organisms into nature, including field trials, in order to prevent these new technologies from being released prematurely and to uphold the precautionary principle, which is enshrined in the Treaty on the Functioning of the European Union as well as the CBD“.
Fine-scale estimation of key life-history parameters of malaria vectors: implications for next-generation vector control technologies
17329A. L. Morris, A. Ghani and N. Ferguson, Parasites and Vectors, 14:311. 2021-06-08 14:48:41.
Mosquito control has the potential to significantly reduce malaria burden on a region, but to influence public health policy must also show cost-effectiveness. Gaps in our knowledge of mosquito population dynamics mean that mathematical modelling of vector control interventions have typically made simplifying assumptions about key aspects of mosquito ecology. Often, these assumptions can distort the predicted efficacy of vector control, particularly next-generation tools such as gene drive, which are highly sensitive to local mosquito dynamics.
Living With the Limits of Our New Clerisy’s Knowledge
17306R. Fernandez, PJ Media, 2021-06-08 11:22:01.
We are living in a strange time when reason has fallen short of human expectations and there is, once again, pressure to place our trust in faith. Leighton Woodhouse hit the nail on the head when he argued that we have appointed a New Clerisy to rule over us, not because they are infallible but to save ourselves from the tide of uncertainty that seems to have engulfed our once seemingly confident global world. Unfortunately, the new clergy seem too fallible to take on trust. They flip-flop on expert advice and one scientist denounces the other on YouTube. Once things seemed more cut and dried. Once we were at the End of History. Science could predict the future more or less and the public hoped with increasing accuracy. Ever since the 17th century, the expectation was that the scientific revolution would supply the answers. As the frontier moved from the simple, computable problems of the early 20th century to complex systems — of which biotechnology, artificial intelligence, social networks, and eco-engineering are prime examples — they began to involve the management of uncertainty because it was difficult to control all the variables involved. The care with which some scientists have approached the subject of gene drives, a biological technology as powerful as “gain of function,” illustrates the challenges of dealing with uncertainties.
Victory: NSW Government Invests in Humane Mice Control!
17224PETA Australia, PETA Australia, 2021-06-05 16:21:19.
Just two weeks after calling us “brainless” for suggesting that the state government invest in more ethical, eco-friendly methods of mice control – Minister for Agriculture Adam Marshall announced a $1.8 million package to “fast-track the delivery of next generation ‘gene drive’ technology to control future plagues”. The money will fund a three-year programme of genetic biocontrol research, led by the University of Adelaide, CSIRO, and the Centre for Invasive Species Solutions, to identify fast-acting gene drives designed to spread an inherited characteristic through a population. The research will test two strategies for population control, including an approach which eliminates sperm carrying the X chromosome, producing more male than female offspring, and a second approach of making female mice infertile. PETA has been talking about immunocontraception methods of controlling invasive animal populations for years, so we’re pleased to see the government is finally using science to tackle this problem in a more ethical and eco-friendly manner. Had it acted sooner, millions of small animals, including non-target species, would have been spared slow and agonising deaths. Last month, the New South Wales government announced it would use a new, strong poison and spruiked it as “napalm” for mice. Leading rodent experts questioned the plan, warning that the poison’s use came with a high risk of killing native and domestic animals as well. Dr Peter Brown, leader of the rodent management research team at CSIRO, told The Guardian, “The anti-coagulants can accumulate up through the food chain, and so birds of prey or other animals can be feeding on dead mice and they could potentially get a lethal dose themselves through secondary poisoning.”
Gene tech to prevent crossbreeding could safely harness the power of gene drives
17212I. l. Guillou, The Science Advisory Board, 2021-06-04 15:52:06.
A new gene engineering technology could allow scientists to harness the benefits of releasing genetically modified animals into the wild without the risk of uncontrolled spread. The new study, published in the journal Nature Communications on June 2, could help in the battle against the spread of diseases like malaria. The advent of the genetic age offers the tantalizing prospect of being able to genetically alter animals, such as pests and disease vectors, to reduce the harm they cause to society. However, any technology with the ability to make a difference on a significant scale would also have the potential to cause serious damage if it went out of control. Gene drives are one such technology. These genetic modifications are designed to spread through a population quickly and rely on the CRISPR-Cas9 gene editing system to make a duplicate copy of the gene drive on the partner chromosome. This means that all offspring inherit the gene, compared to only 50% through normal genetic inheritance. However, there are concerns about the effect of releasing such gene drives into the wild. Unintended consequences, potentially due to mutations or ecological shifts, could be irreversible. This has led geneticists to search for new versions of gene drives that can prevent unrestricted spread by stopping engineered animals from crossbreeding with the wild population. Approaches previously developed have severe limitations, such as not working in multicellular organisms, causing high fitness costs, or working incompletely.
New biocontrol research to help prevent mice plagues
17206Anonymous, The National Tribune, 2021-06-04 15:41:51.
Scientists at the University of Adelaide are partnering with the CSIRO and the Centre for Invasive Species Solutions on breakthrough genetic biocontrol research to help control mice populations and prevent future mice plagues. The three-year research program will identify fast acting gene drives, which are designed to spread an inherited characteristic for population control through mice populations at higher-than-normal rates. This would effectively enable scientists to interrupt the breeding cycle and keep mice populations at manageable levels. The NSW Government will provide $1.8 million towards the project to fast-track the delivery of the ‘gene drive technology’ as part of a range of measures not only to mitigate the impacts of the mice currently across NSW, but also to create options to reduce the impact of future population spikes.
Gene drive could be a game changer for future mouse control.
17214Anonymous, Centre for Invasive Species Solutions, 2021-06-03 16:02:28.
We are proud to announce we will be coordinating a brand new, three-year program of genetic biocontrol research, which will identify fast acting gene drives designed to spread an inherited characteristic through a population at higher-than-normal rates. Using targeted gene drives, scientists aim to interrupt the breeding cycle of mice and potentially other ferals, which could keep populations at manageable levels. The $1.8 million research program will be led by Professor Paul Thomas at our partner organisation the University of Adelaide in collaboration with our member organisation CSIRO. The NSW Minister for Agriculture, Adam Marshall said cutting edge solutions meant future mouse plagues could be extinguished before they begin. This specific research funding will test two strategies for population control and recommend at least one for future suppression of mice. The ‘X-shredder’ approach eliminates sperm carrying the X chromosome, producing more male than female offspring. The ‘female infertility’ approach spreads a genetic modification that would eventually make females infertile. We look forward to seeing the outcomes of this world-class innovative research being led by Aussie scientists.
“Gene Drive” Technology To Control Mouse Invasions | Liverpool City Champion
17208T. Carrington, Liverpool IL, 2021-06-03 15:45:57.
As western New South Wales faces a devastating mouse plague, the government is investing in groundbreaking genetic biocontrol research that could transform pest management in Australia. Agriculture Minister Adam Marshall said the NSW government will provide $ 1.8 million for the project to accelerate delivery of next-generation ‘gene drive’ technology to control future plagues. “The government has invested $ 50 million in a range of supportive measures, not only to mitigate the impacts of the mice that are currently crawling across much of New South Wales, but also to create options to reduce l ‘impact of future population peaks, “he said. Thursday. Until now, farmers had to rely on baiting and trapping to control mouse infestations, but the government is now “accelerating critical research to bring mouse control into the 21st century,” he said. declared. The three-year genetic biocontrol research program will identify fast-acting gene drives that are designed to spread an inherited trait through a population at above normal rates.
Australia plots biological warfare to eradicate rampaging ‘mouse plague’
17204J. Smyth, Financial Times, 2021-06-03 15:37:11.
Australia is home to some of the world’s most fearsome creatures. But none is more destructive than the humble house mouse, a plague of which is rampaging across vast swaths of farmland and terrorising countryfolk. Farmers in New South Wales, the worst affected state, warned the furry critters could cost them A$1bn ($765m) in lost crops and poison baits this season. Residents in rural towns have been fighting a six-month battle against the army of wild house mice, which has gnawed through wiring on home appliances, polluted water supplies and even bitten patients in hospital beds. Scientists said the plague was bolstered by favourable weather conditions after years of drought and the nation’s second biggest grain harvest on record. State authorities have proposed “napalming” the mice by allowing farmers to use the poison bromadiolone against the mice, which has ignited a furious debate over its environmental impact.
Scientists design new gene drive to stop the transmission of devastating diseases
17292E. Henderson, AZO Life Sciences, 2021-06-03 10:42:37.
CRISPR-based technologies offer enormous potential to benefit human health and safety, from disease eradication to fortified food supplies. As one example, CRISPR-based gene drives, which are engineered to spread specific traits through targeted populations, are being developed to stop the transmission of devastating diseases such as malaria and dengue fever. But many scientists and ethicists have raised concerns over the unchecked spread of gene drives. Once deployed in the wild, how can scientists prevent gene drives from uncontrollably spreading across populations like wildfire? Now, scientists at the University of California San Diego and their colleagues have developed a gene drive with a built-in genetic barrier that is designed to keep the drive under control. Led by molecular geneticist Omar Akbari's lab, the researchers engineered synthetic fly species that, upon release in sufficient numbers, act as gene drives that can spread locally and be reversed if desired.
Mouse plague control hopes raised with funding for genetic biocontrol research
17289Anonymous, From Press, 2021-06-03 10:36:25.
As communities and farmers continue to battle the mouse plague, a funding announcement for genetic biocontrol research could be a potential game changer for future plagues. The New South Wales government has today announced a $50 million mouse control package which includes $1.8 million dollars in funding for genetic control of mice populations. The project aims to fast-track the delivery of next generation "gene drive" technology to control plagues of the future. Researchers have welcomed the announcement, including Australia's lead researcher Professor Paul Thomas from the University of Adelaide. He said the technology is only relatively new, having been developed to some extent for insects and malaria control, but has not yet been applied to mammals. "So effectively it just uses the natural mating processes to spread a gene though a population that will cause, [and] what we are trying to cause, female [mouse] infertility," he said. "We have modelled it already and that should cause the population to crash over time. "This boost of funding will enable us to move much faster on these projects."Another control approach will also be investigated, the "X-shredder" approach, which eliminates sperm carrying the X chromosome, producing more male than female offspring.
Genetically modified mosquitoes and Africa
17194S. Bagcchi, Sci Dev Net, 2021-06-02 20:30:12.
The World Health Organization (WHO) has released new guidance for the deployment of genetically modified (GM) mosquitoes to combat vector-borne diseases like malaria and dengue. GM mosquitoes may carry a gene that kills female progeny and the technology can be used against the Aedes aegypti mosquito that carries dengue, chikungunya and Zika viruses. For malaria, genetic modification has focused on reducing the ability of the female Anopheles mosquito to carry the parasite that causes the disease. The WHO guidance, released this month, relates to research and development of GM mosquitoes as well as issues around effectiveness, safety, affordability and ethics. GDN awards advert finalised Presently, measures against mosquito vectors include the use of insecticides and elimination of the breeding spots of mosquito larva, said the guidance, developed in partnership with WHO collaborators such as the Special Programme for Research and Training in Tropical Diseases and the GeneConvene Global Collaborative.
ISAAA Webinar: What is Gene Drive?
17188ISAAA, ISAAA, 2021-06-02 20:19:58.
ISAAA, in partnership with the Outreach Network for Gene Drive Research and the Biotechnology Information Centers, will be conducting the Gene Drive Webinar Series. The first webinar titled What is Gene Drive? will be held on June 10, 2021, at 2 PM GMT+8 (7 AM London/4 PM Sydney) via Zoom. The potential uses and impacts of gene drive technologies are a topic of growing interest at the international and national levels in many countries. The Gene Drive Webinar Series aims to help promote a productive and balanced conversation on the benefits and risks of possible gene drive applications, providing factual and accurate information that can help place the discussion under the Convention on Biological Diversity in context.
‘Gene drive’ tech to control mice plagues
17219AAP, Countryman, 2021-06-02 16:11:50.
As western NSW deals with a devastating mouse plague the government is investing in breakthrough genetic biocontrol research that could transform pest management in Australia. Agriculture Minister Adam Marshall said the NSW government would provide $1.8 million to the project to fast-track the delivery of next generation 'gene drive' technology to control future plagues. "The government has invested $50 million in a range of support measures, not only to mitigate the impacts of the mice currently crawling across so much of NSW, but also to create options to ensure we reduce the impact of future population spikes," he said on Thursday. Until now farmers have had to rely on baiting and trapping to control mouse infestations but the government was now "fast-tracking critical research to bring mouse control into the 21st century", he said. The three-year program of genetic biocontrol research will identify fast acting gene drives which are designed to spread an inherited characteristic through a population at higher-than-normal rates. Mr Marshall said it would also investigate the transferability of the technology to other pest species such as black rats, rabbits and feral cats using advanced computer modelling.
New CRISPR Tools Can Help Contain Mosquito Disease Transmission
17191Anonymous, labcompare, 2021-06-01 20:26:34.
Scientists have now developed several genetic editing tools that help pave the way to an eventual gene drive designed to stop Culex mosquitoes from spreading disease. As detailed in the journal Nature Communications, Xuechun Feng, Valentino Gantz and their colleagues at Harvard Medical School and National Emerging Infectious Diseases Laboratories developed a Cas9/guide-RNA expression "toolkit" designed for Culex mosquitoes. Since such little attention in genetic engineering has been devoted to Culex mosquitoes, the researchers were required to develop their toolkit from scratch, starting with a careful examination of the Culex genome. While Culex mosquitoes are less problematic in the United States, they are much more of a health risk in Africa and Asia, where they transmit the worm causing filariasis, a disease that can lead to a chronic debilitating condition known as elephantiasis. The researchers also demonstrated that their tools could work in other insects.
African Experts Welcome WHO Guidance on Ethics, Standards, and Governance of Genetically Modified Mosquito Research
17200E. Nakkazi, Health Policy Watch, 2021-06-01 15:24:31.
Researchers engaged in mosquito gene drive technologies are optimistic that new World Health Organization (WHO) guidance on best research practices will ensure that their work is safe and ethical. Such guidance also helps research results advance from laboratories to be used in the field, the researchers told Health Policy Watch. Due to limiting regulatory frameworks, most African countries doing research on genetically modified mosquitoes have been accused of carrying out unethical research. Some confine their work to laboratories because regulations mostly focus on handling plant-based genetically modified organisms. The WHO recently released essential standards for the study and evaluation of genetically modified mosquitoes so use of this public health tool can be ethical, effective, and affordable. Malaria kills more than 400,000 people a year worldwide. “Genetically modified mosquitoes are one of a number of promising new tools that could help speed the pace of progress against malaria and other vector-borne diseases,” WHO Global Malaria Programme Director Dr Pedro Alonso said.
What is wrong in extinguishing a species? Charting the Ethical Challenges of using Gene-Drive Technologies to eradicate A. gambiae vector populations
17161M. Annoni and T. Pievani, Biolaw Journal-Rivista Di Biodiritto, 2021-05-31 19:04:09.
This article analyses three ethical arguments against the use of gene-drive technologies to control for, and possibly extinguish, a particular species of vector mosquitoes (Anopheles gambiae) causing the malaria infection. We conclude that none of these arguments is truly persuasive in the specific case and, therefore, that using gene-drive technologies to suppress or eradicate the population of Anopheles gambiae could be ethically justifiable provided certain cautions referring to ecological consequences, evolutionary effects and social engagement of local communities.
Analysis of off-target effects in CRISPR-based gene drives in the human malaria mosquito
17141W. T. Garrood, N. Kranjc, K. Petri, D. Y. Kim, J. A. Guo, A. M. Hammond, I. Morianou, V. Pattanayak, J. K. Joung, A. Crisanti and A. Simoni, Proceedings of the National Academy of Sciences, 118:e2004838117. 2021-05-31 13:24:14.
CRISPR-Cas9 nuclease-based gene drives have been developed toward the aim of control of the human malaria vector Anopheles gambiae. Gene drives are based on an active source of Cas9 nuclease in the germline that promotes super-Mendelian inheritance of the transgene by homology-directed repair (“homing”). Understanding whether CRISPR-induced off-target mutations are generated in Anopheles mosquitoes is an important aspect of risk assessment before any potential field release of this technology. We compared the frequencies and the propensity of off-target events to occur in four different gene-drive strains, including a deliberately promiscuous set-up, using a nongermline restricted promoter for SpCas9 and a guide RNA with many closely related sites (two or more mismatches) across the mosquito genome. Under this scenario we observed off-target mutations at frequencies no greater than 1.42%. We witnessed no evidence that CRISPR-induced off-target mutations were able to accumulate (or drive) in a mosquito population, despite multiple generations’ exposure to the CRISPR-Cas9 nuclease construct. Furthermore, judicious design of the guide RNA used for homing of the CRISPR construct, combined with tight temporal constriction of Cas9 expression to the germline, rendered off-target mutations undetectable. The findings of this study represent an important milestone for the understanding and managing of CRISPR-Cas9 specificity in mosquitoes, and demonstrates that CRISPR off-target editing in the context of a mosquito gene drive can be reduced to minimal levels.All raw amplicon sequencing files have been deposited in the National Center for Biotechnology Information (NCBI) BioProject (accession code PRJNA665154).
Experimental demonstration of tethered gene drive systems for confined population modification or suppression
17153M. Metzloff, E. Yang, S. Dhole, A. G. Clark, P. W. Messer and J. Champer, bioRxiv, 2021.05.29.446308. 2021-05-30 10:50:23.
Tethered drive systems, in which a locally confined gene drive provides the CRISPR nuclease needed for a homing drive, could provide a solution to this problem, offering the power of a homing drive and confinement of the supporting drive. Here, we demonstrate the engineering of a tethered drive system in Drosophila, using a TARE drive to support modification and suppression homing drives. Each drive was able to bias inheritance in its favor, and the TARE drive was shown to spread only when released above a threshold frequency in experimental cage populations. After the TARE drive had established in the population, it facilitated the spread of a subsequently released split homing modification drive (to all individuals in the cage) and of a homing suppression drive (to its equilibrium frequency). Our results show that the tethered drive strategy is a viable and easily engineered option for providing confinement of homing drives to target populations. Competing Interest StatementThe authors have declared no competing interest.
Improving mosquito control strategies with population genomics
18781T. L. Schmidt, N. M. Endersby-Harshman and A. A. Hoffmann, Trends in Parasitology, 37:907-921. 2021-05-29 12:41:38.
Mosquito control strategies increasingly apply knowledge from population genomics research. This review highlights recent applications to three research domains: mosquito invasions, insecticide resistance evolution, and rear and release programs. Current research trends follow developments in reference assemblies, either as improvements to existing assemblies (particularly Aedes) or assemblies for new taxa (particularly Anopheles). With improved assemblies, studies of invasive and rear and release target populations are better able to incorporate adaptive as well as demographic hypotheses. New reference assemblies are aiding comparisons of insecticide resistance across sister taxa while helping resolve taxon boundaries amidst frequent introgression. Anopheles gene drive deployments and improved Aedes genome assemblies should lead to a convergence in research aims for Anopheles and Aedes in the coming years.
WHO releases new guidance for deployment of genetically modified mosquitoes
17130E. Henderson, News Medical Life Sciences, 2021-05-28 19:13:57.
The World Health Organization (WHO) has released new guidance for the deployment of genetically modified (GM) mosquitoes to combat vector-borne diseases like malaria and dengue. GM mosquitoes may carry a gene that kills female progeny and the technology can be used against the Aedes aegypti mosquito that carries dengue, chikungunya and Zika viruses. For malaria, genetic modification has focused on reducing the ability of the female Anopheles mosquito to carry the parasite that causes the disease. The WHO guidance, released this month, relates to research and development of GM mosquitoes as well as issues around effectiveness, safety, affordability and ethics. Presently, measures against mosquito vectors include the use of insecticides and elimination of the breeding spots of mosquito larva, said the guidance, developed in partnership with WHO collaborators such as the Special Programme for Research and Training in Tropical Diseases and the GeneConvene Global Collaborative.
Researchers Create New CRISPR Tools to Help Contain Mosquito Disease Transmission
18225M. Aguilera, UC San Diego News Center, 2021-05-28 15:43:14.
Much less genetic engineering has been devoted to Culex genus mosquitoes, which spread devastating afflictions stemming from West Nile virus—the leading cause of mosquito-borne disease in the continental United States—as well as other viruses such as the Japanese encephalitis virus (JEV) and the pathogen causing avian malaria, a threat to Hawaiian birds.University of California San Diego scientists have now developed several genetic editing tools that help pave the way to an eventual gene drive designed to stop Culex mosquitoes from spreading disease. Gene drives are designed to spread modified genes, in this case those that disable the ability to transmit pathogens, throughout the targeted wild population.As detailed in the journal Nature Communications, Xuechun Feng, Valentino Gantz and their colleagues at Harvard Medical School and National Emerging Infectious Diseases Laboratories developed a Cas9/guide-RNA expression “toolkit” designed for Culex mosquitoes. Since such little attention in genetic engineering has been devoted to Culex mosquitoes, the researchers were required to develop their toolkit from scratch, starting with a careful examination of the Culex genome.
New CRISPR tools help contain mosquito disease transmission: Genetics toolkit targets less researched Culex mosquitoes, which transmit West Nile virus and avian malaria.
17145University of California - San Diego, ScienceDaily, 2021-05-28 13:29:00.
Since the onset of the CRISPR genetic editing revolution, scientists have been working to leverage the technology in the development of gene drives that target pathogen-spreading mosquitoes such as Anopheles and Aedes species, which spread malaria, dengue and other life-threatening diseases. Much less genetic engineering has been devoted to Culex genus mosquitoes, which spread devastating afflictions stemming from West Nile virus -- the leading cause of mosquito-borne disease in the continental United States -- as well as other viruses such as the Japanese encephalitis virus (JEV) and the pathogen causing avian malaria, a threat to Hawaiian birds. University of California San Diego scientists have now developed several genetic editing tools that help pave the way to an eventual gene drive designed to stop Culex mosquitoes from spreading disease. Gene drives are designed to spread modified genes, in this case those that disable the ability to transmit pathogens, throughout the targeted wild population.
The origin of island populations of the African malaria mosquito, Anopheles coluzzii
17287M. Campos, M. Hanemaaijer, H. Gripkey, T. C. Collier, Y. S. Lee, A. J. Cornel, J. Pinto, D. Ayala, H. Rompao and G. C. Lanzaro, Communications Biology, 4:9. 2021-05-26 10:26:11.
Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome study of 142 specimens from nine countries in continental Africa and three islands in the Gulf of Guinea. This sample set covers a large part of this species' geographic range. Our population genomic analyses included a description of the structure of mainland populations, island populations, and connectivity between them. Three genetic clusters are identified among mainland populations and genetic distances (F-ST) fits an isolation-by-distance model. Genomic analyses are applied to estimate the demographic history and ancestry for each island. Taken together with the unique biogeography and history of human occupation for each island, they present a coherent explanation underlying levels of genetic isolation between mainland and island populations. We discuss the relationship of our findings to the suitability of Sao Tome and Principe islands as candidate sites for potential field trials of genetic-based malaria control strategies. Campos, Lanzaro and colleagues use whole-genome sequencing and population genomic analyses to infer connectivity between mainland and island mosquito populations in West Africa. The unique biogeographic history for each island population is reported, and the findings highlight potential candidate sites for genetic-based malaria control strategies.
Pest reduction with female killers and sterile males
17114L. Mertz, Good Fruit Grower, 2021-05-25 18:40:52.
New ways to fight spotted wing drosophila are in the works, thanks to new genetic engineering tools. These transgenic methods introduce new reproduction-hampering genes into male SWD, so that when they mate with females, the females either don’t have any young, or their female young die early in their development. The approach falls under the umbrella of sterile insect technique (SIT), which has traditionally been done with radiation to sterilize males that are then released to reduce pest reproduction. “SITs are thought of as green technologies, because they are species-specific, they have the advantage that the control agent is the insect itself, and they reduce the dependence on insecticides,” said Max Scott, a professor of entomology at North Carolina State University who is developing one of these approaches. He and his research group have incorporated a female-killing gene into male SWD. In a different approach, the San Diego company Agragene is advancing technology first developed by University of California, San Diego researchers. Here, the project makes use of an advanced gene-editing tool — called CRISPR — to add genes that both kill females and sterilize males. “We really do believe that our technology will bring a sea change to what’s going on out there,” said Gordon Alton, president and CEO of Agragene Inc. If all goes well, he anticipates growers will have access to the technology within two to three years
Q&A: WHO updates guidance on testing genetically modified mosquitoes
17135E. N. Dreisbach, Healio, 2021-05-24 13:04:56.
Researchers have been exploring the use of genetically modified mosquitos as a potential control method for vector-borne diseases. Just last month, Oxitec began releasing its genetically modified (GM), self-limiting male Aedes aegypti mosquitoes in the Florida Keys in the hope of reducing the mosquito population.This month, WHO released the second edition of its guidance for testing GM mosquitos (GMMs), updating guidelines that were originally released in 2014. We spoke with Jan Kolaczinski, PhD, MSc, head of the vector control and insecticide resistance unit in WHO’s Global Malaria Program, about the new guidance and what it means for researchers.
Why the EU should back research into gene drive – even if Europe never uses it
17132R. Müller, The Brussels Times, 2021-05-23 12:00:13.
As the EU’s Biodiversity Strategy reaches the European Parliament, it has reopened a worrying debate about research into gene drive technology, a tool which could pave the way for biasing the inheritance of desired genetic traits through targeted species. Advances in this kind of genetic technology could allow scientists to create a blueprint for stopping diseases spread by mosquitoes and protecting endangered species, both significant reasons for supporting this emerging field. Yet even if EU decision makers see no need for gene drive technology in Europe at present, there are compelling reasons for supporting ongoing research, and rejecting irresponsible and short-sighted calls for a moratorium. Firstly, the threat of malaria and other mosquito-borne diseases may be minimal today but it existed on the continent within living memory, with Europe first becoming malaria-free in 1975, and then again only as recently as 2015.
Scientists want to alter rodent genes to prevent mice plagues
17092P. Hannon, The Sydney Morning Herald, 2021-05-23 10:52:32.
Mice plagues, such as the one ravaging parts of inland NSW, could become a thing of the past if scientists succeed in modifying the genes of the rodents so that populations crash before they can take off. Paul Thomas, a researcher at the University of Adelaide, is part of an international consortium including the CSIRO and the US Department of Agriculture, studying how to safely alter genes to make female mice infertile. The techniques learned could potentially be applied to other damaging invasive mammals such as cats and foxes.
Malaria-Resistant Mosquitoes (Diptera: Culicidae); The Principle is Proven, But Will the Effectors Be Effective?
18710Z. N. Adelman and B. B. Kojin, Journal of Medical Entomology, 58:1997-2005. 2021-05-21 13:50:24.
Over the last few decades, a substantial number of anti-malarial effector genes have been evaluated for their ability to block parasite infection in the mosquito vector. While many of these approaches have yielded significant effects on either parasite intensity or prevalence of infection, just a few have been able to completely block transmission. Additionally, many approaches, while effective against the parasite, also disrupt or alter important aspects of mosquito physiology, leading to corresponding changes in lifespan, reproduction, and immunity. As the most promising approaches move towards field-based evaluation, questions of effector gene robustness and durability move to the forefront. In this forum piece, we critically evaluate past effector gene approaches with an eye towards developing a deeper pipeline to augment the current best candidates.
Genetically modified mosquitoes; WHO issues new guidance for research
17084DTE Staff, Down To Earth, 2021-05-20 15:10:16.
Genetically-modified mosquitoes or GMMs have been used across the world to control mosquitoes. GMMs have been able to bring down the population of the Aedes aegypti by 90 per cent in countries like Brazil, the Cayman Islands, Panama and Malaysia. But there have never been any global protocols or standards on the breeding of GMMs. The World Health Organization has addressed this by setting essential standards for the research and development of GMMs. These standards are mainly about ethics, safety, affordability and effectiveness of GMMS. GMMs are male mosquitoes modified to carry a lethal gene. When they mate, the genes get passed on to their offspring. The gene prevents female offspring from building an essential protein and causes them to die before reaching maturity. GMMs could become a cost-effective and powerful tool to control mosquitoes. Over 40,000 people die from malaria and 100-400 million people get infected with dengue each year. They can reach mosquito populations and mosquito larval breeding sites that are currently expensive and difficult to reach. It can target specific mosquito species and thus avoid the ecological and environmental hazards of usual insecticides.
Burkina Faso Testing Genetically Modified Mosquitoes to Curb Malaria
17082H. Wilkins, Voice of America, 2021-05-20 15:06:44.
The mosquito-borne disease malaria kills more than 400,000 people each year, the vast majority in Africa. Target Malaria, an international group of scientists, is working in Burkina Faso on a genetic solution. Abdoulaye Diabate, with the West African country’s Research Institute for Science and Health, said the objective of Target Malaria is to develop a genetic control tool specifically applied to mosquitoes to be able to drastically reduce or eliminate the density of mosquitoes. The scientists are genetically modifying mosquitoes so their offspring will be only male, and any females they mate with after release will also produce just males. Since only female mosquitoes spread malaria, the disease should drop off quickly along with their population. In village of Bana, where the genetically modified mosquitoes were first tested in 2019, locals were initially worried about the experiment. Kiesiara Sanou, a Bana village elder, said that at the beginning, people thought the survey would release mosquitoes in the village that could cause more diseases. But since working with Target Malaria, they’ve come to understand exactly what the purpose is and now even help them with tasks like collecting the mosquitoes. Genetically modified mosquitoes are just one malaria solution that has been tested in Burkina Faso. The country also pioneered pesticide-infused mosquito nets.
Optimized CRISPR tools and site-directed transgenesis towards gene drive development in Culex quinquefasciatus mosquitoes
17147X. Feng, V. López Del Amo, E. Mameli, M. Lee, A. L. Bishop, N. Perrimon and V. M. Gantz, Nature Communications, 12:2960. 2021-05-20 13:34:20.
Culex mosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control of Culex mosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking in Culex. Here, we develop a Culex-specific Cas9/gRNA expression toolkit and use site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We show that gRNA scaffold variants improve transgenesis efficiency in both Culex quinquefasciatus and Drosophila melanogaster and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.
WHO issues new guidance for research on genetically modified mosquitoes to fight malaria and other vector-borne diseases
17076WHO, reliefweb, 2021-05-19 14:55:10.
New guidance from the World Health Organization (WHO) sets essential standards to inform future research and development on genetically modified mosquitoes, particularly in addressing issues relating to ethics, safety, affordability and effectiveness. Malaria and other vector-borne diseases, including dengue and Zika, affect millions globally. More than 400 000 people a year die from malaria alone. If proven safe, effective and affordable, genetically modified vector mosquitoes could be a valuable new tool to fight these diseases and eliminate their enormous health, social and economic burden. The guidance framework for testing genetically modified mosquitoes, developed in partnership with TDR, the Special Programme for Research and Training in Tropical Diseases, and the GeneConvene Global Collaborative, an initiative of the Foundation for the National Institutes of Health, describes best practices to ensure that the study and evaluation of genetically modified mosquitoes as public health tools is safe, ethical and rigorous. Current strategies for limiting transmission of mosquito-borne diseases are only partially effective. New, complementary approaches are needed to close the gaps in current vector control interventions, such as effective control of outdoor biting, and to provide alternatives to manage the increasing threat of insecticide resistance. Research suggests genetically modified mosquitoes could be a powerful and cost-effective tool to supplement existing interventions.
Targeting conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus
17054M. Walter, R. Perrone and E. Verdin, Journal of virology, 2021-05-19 13:32:53.
Here, we analyze in cell culture experiments the evolution of resistance in a viral gene drive against human cytomegalovirus. We report that, after an initial invasion of the wildtype population, a drive-resistant population is positively selected over time and outcompetes gene drive viruses. However, we show that targeting evolutionary conserved sequences ensures that drive-resistant viruses acquire long-lasting mutations and are durably attenuated. As a consequence, and even though engineered viruses do not stably persist in the viral population, remaining viruses have a replication defect, leading to a long-term reduction of viral levels. This marks an important step toward developing effective gene drives in herpesviruses, especially for therapeutic applications.<b>Importance</b>The use of defective viruses that interfere with the replication of their infectious parent after co-infecting the same cells - a therapeutic strategy known as viral interference - has recently generated a lot of interest. The CRISPR-based system that we recently reported in herpesviruses represents a novel interfering strategy that causes the conversion of wildtype viruses into new recombinant viruses and drives the native viral population to extinction. In this report, we analyzed how targeted viruses evolved resistance against the technology. Through numerical simulations and cell culture experiments with human cytomegalovirus, we show that, after the initial propagation, a resistant viral population is positively selected and outcompetes engineered viruses over time. We show however that targeting evolutionary conserved sequences ensures that resistant viruses are mutated and attenuated, which leads to a long-term reduction of viral levels. This marks an important step toward the development of novel therapeutic strategies against herpesviruses.
Guidance framework for testing of genetically modified mosquitoes, second edition
17049WHO, WHO-TDR, 2021-05-19 10:41:03.
For more than 2 decades, scientists have been working to harness the promise of molecular biology to develop genetically modified mosquitoes (GMMs) for use as public health tools to prevent the transmission of vector-borne diseases. Responding to a need for additional standards and guidance, the WHO Special Programme for Research and Training in Tropical Diseases (WHO-TDR) and the Foundation for the National Institutes of Health (FNIH) published in 2014 the first WHO Guidance framework for testing genetically modified mosquitoes. This revised version takes into account the technical progress made and lessons learned in this rapidly advancing field of research. Like the original guidance framework, it is intended to provide standards that foster quality and consistency in the processes for developing, testing and regulating these new genetic technologies. Best practices recommended in the 2021 guidance framework will further contribute to the comparability of results and credibility of conclusions in order to facilitate decision-making by countries interested in the potential use of GMMs as public health tools for the control of vector-borne diseases.
Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes
17068R. Carballar-Lejarazú, T. B. Pham, V. Bottino-Rojas, A. Adolfi and A. A. James, J Vis Exp, 2021-05-18 14:30:01.
Control of mosquito-borne pathogens using genetically-modified vectors has been proposed as a promising tool to complement conventional control strategies. CRISPR-based homing gene drive systems have made transgenic technologies more accessible within the scientific community. Evaluation of transgenic mosquito performance and comparisons with wild-type counterparts in small laboratory cage trials provide valuable data for the design of subsequent field cage experiments and experimental assessments to refine the strategies for disease prevention. Here, we present three different protocols used in laboratory settings to evaluate transgene spread in anopheline mosquito vectors of malaria. These include inundative releases (no gene-drive system), and gene-drive overlapping and non-overlapping generation trials. The three trials vary in a number of parameters and can be adapted to desired experimental settings. Moreover, insectary studies in small cages are part of the progressive transition of engineered insects from the laboratory to open field releases. Therefore, the protocols described here represent invaluable tools to provide empirical values that will ultimately aid field implementation of new technologies for malaria elimination.
Genetic Technologies for Sustainable Management of Insect Pests and Disease Vectors
17157S. Grilli, R. Galizi and C. Taxiarchi, Sustainability, 13. 2021-05-18 11:00:25.
Recent advancements in genetic and genome editing research, augmented by the discovery of new molecular tools such as CRISPR, have revolutionised the field of genetic engineering by enabling precise site-specific genome modifications with unprecedented ease. These technologies have found a vast range of applications, including the development of novel methods for the control of vector and pest insects. According to their genetic makeup and engineering, these tools can be tuned to impose different grades of impact on the targeted populations. Here, we review some of the most recent genetic control innovations under development, describing their molecular mechanisms and performance, highlighting the sustainability potentials of such interventions.
New genetic copycatchers detect efficient and precise CRISPR editing in a living organism
17013UNIVERSITY OF CALIFORNIA - SAN DIEGO, UNIVERSITY OF CALIFORNIA - SAN DIEGO, 2021-05-11 12:55:38.
Researchers at the University of California San Diego have laid the groundwork for a potential new type of gene therapy using novel CRISPR-based techniques. Working in fruit flies and human cells, research led by UC San Diego Postdoctoral Scholar Zhiqian Li in Division of Biological Sciences Professor Ethan Bier's laboratory demonstrates that new DNA repair mechanisms could be designed to address the effects of debilitating diseases and damaged cell conditions. The scientists developed a novel genetic sensor called a "CopyCatcher," which capitalizes on CRISPR-based gene drive technology, to detect instances in which a genetic element is copied precisely from one chromosome to another throughout cells in the body of a fruit fly.
CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion
17008Z. Li, N. Marcel, S. Devkota, A. Auradkar, S. M. Hedrick, V. M. Gantz and E. Bier, Nature Communications, 12:2625. 2021-05-11 12:45:39.
CRISPR-based active genetic elements, or gene-drives, copied via homology-directed repair (HDR) in the germline, are transmitted to progeny at super-Mendelian frequencies. Active genetic elements also can generate widespread somatic mutations, but the genetic basis for such phenotypes remains uncertain. It is generally assumed that such somatic mutations are generated by non-homologous end-joining (NHEJ), the predominant double stranded break repair pathway active in somatic cells. Here, we develop CopyCatcher systems in Drosophila to detect and quantify somatic gene conversion (SGC) events. CopyCatchers inserted into two independent genetic loci reveal unexpectedly high rates of SGC in the Drosophila eye and thoracic epidermis. Focused RNAi-based genetic screens identify several unanticipated loci altering SGC efficiency, one of which (c-MYC), when downregulated, promotes SGC mediated by both plasmid and homologous chromosome-templates in human HEK293T cells. Collectively, these studies suggest that CopyCatchers can serve as effective discovery platforms to inform potential gene therapy strategies.
Cloning wildlife and editing their genes to protect them and us.
16982H. Thomasy, NEO-LIFE, 2021-05-06 16:06:20.
In December 10, 2020, Elizabeth Ann made history just by being born. She isn’t a British royal, an American married to a British royal, a movie star’s daughter, or even human for that matter. Elizabeth Ann is a ferret—but perhaps the most famous ferret of all time. More specifically, she is the clone of a black-footed ferret named Willa who has been dead for more than 30 years. Elizabeth Ann’s momentous birth marks the first successful cloning of an endangered species native to North America (endangered species like the gaur, or Indian bison, and the mouflon, a wild sheep originally found in Corsica and Sardinia, have been cloned previously). If she can breed successfully, Elizabeth Ann will add valuable genetic diversity to the very small estimated population of around 600 remaining black-footed ferrets, which are all descended from just seven animals. But low genetic diversity isn’t the only thing standing in the way of these ferrets making a comeback. The other major threat is disease. Diseases are a huge problem for many endangered species, but, as the previous year has emphasized all too well, diseases that circulate in animals can also have disastrous consequences if they jump to humans. Genetic engineering of animals in the wild might offer us a way to protect not only our furry friends and feathered compadres, but ourselves as well. Although still in the early stages of research, scientists around the world are working on numerous projects to engineer animals to be resistant to diseases that can impact humans as well, including plague, Lyme disease, dengue fever, and Zika.
Driving genetic destruction
16899Anonymous, Alliance for Natural Health, 2021-04-29 17:41:37.
Genetically-engineered (GE) mosquitoes have been released in a number of countries, including the US. We’ve known for some time that these experiments have not gone to plan, but a new paper provides a better understanding of how they’ve went awry, and provides a harrowing warning for what could go wrong with a new era of gene editing known as “gene drives” in which the genetics of entire species can be tampered with. This could create a nightmare scenario where, instead of a disease-carrying mosquito population being controlled or eliminated, unpredicted changes occur that make them even more virulent and dangerous. Current GE experiments involve altering the genetics of mosquitoes to be “self-limiting,” meaning that offspring inherit a gene that prevents them from surviving to adulthood, thus driving the population down. The goal is to limit the spread of diseases like dengue and yellow fever. But what has happened is that a certain percentage of the offspring of the GE mosquitoes are surviving and integrating into the gene pool of the local population. Scientists note this will have unpredictable consequences and could lead to more pathogenic disease strains—the very opposite of what these experiments were supposed to accomplish.
Selection of Sites for Field Trials of Genetically Engineered Mosquitoes with Gene Drive
16932G. C. Lanzaro, M. Campos, M. Crepeau, A. Cornel, A. Estrada, H. Gripkey, Z. Haddad, A. Kormos, S. Palomares and W. Sharpee, bioRxiv, 2021.04.28.441877. 2021-04-28 15:53:05.
Novel malaria control strategies using genetically engineered mosquitoes (GEMs) are on the horizon. Population modification is one approach wherein mosquitoes are engineered with genes rendering them refractory to the malaria parasite coupled with a low-threshold, Cas9-based gene drive. When released into a wild vector population, GEMs preferentially transmit these beneficial genes to their offspring, ultimately modifying a vector population into a non-vector one. Deploying this technology awaits evaluation including ecologically contained field trials. Here, we consider a process for site selection, the first critical step in designing a trial. Our goal is to identify a site that maximizes prospects for success, minimizes risk, and serves as a fair, valid, and convincing test of efficacy and impacts of a GEM product intended for large-scale deployment in Africa. We base site selection on geographical, geological, and biological, rather than social or legal, criteria. We recognize the latter as critically important but not preeminent. We propose physical islands as being the best candidates for a GEM field trial and present an evaluation of 22 African islands. We consider geographic and genetic isolation, biological complexity, island size, topography, and identify two island groups that satisfy key criteria for ideal GEM field trial sites.Competing Interest StatementThe authors have declared no competing interest.
Does Gene Technology Offer Potential to Wipe Out Malaria?
16845Anonymous, AFIDEP, 2021-04-25 13:15:13.
The persisting high numbers of Malaria deaths and illnesses mean that the current tools will not get us to zero Malaria. For this reason, experts have continued to explore new tools for Malaria elimination. The gene drive technology is one of the tools being explored for Malaria elimination in Africa. The technology, developed in the past decade, enables precise editing of the genes of living organisms. For Malaria, the technology could be applied to modify the genes of Malaria-causing mosquitoes (the Anopheles) to either reduce their survival or deactivate genes that enable them to carry the Malaria parasite. If successfully applied, scientists believe that gene drive mosquitoes could significantly accelerate the path to Malaria elimination, or zero Malaria. In 2017, the African Union recognized the potential of the gene drive technology in controlling and eliminating Malaria on the continent, and committed to invest in the development and regulation of the technology. This commitment is being implemented by the African Union Development Agency (AUDA/NEPAD), which is currently spearheading efforts to build capacity and support countries to establish the necessary regulatory framework for guiding the research to test the gene drive technology for elimination of Malaria on the continent.
Major fly pest genetically modified in lab to produce more males
16835H. Dunning, Imperial College London, 2021-04-23 14:29:07.
It has been predicted that the world's population will increase to over nine billion people by 2050, and that global food production will need to increase by around 70 percent to match this rate of change. Lead researcher Dr Angela Meccariello, from the Department of Life Sciences at Imperial, said: “Currently, medfly infestations are estimated to contribute towards a loss of up $298 US million annually due to crop damage across a wide geographic area and in over 250 different species of fruits and vegetables. “Due to factors such as climate change, the spread of invasive species and pesticide resistance, there is potential for the negative impact of the medfly on global agriculture to increase if left unchecked. We therefore need new technologies to fight these pests, and our modification could be one such tool.” The team’s modification works by using a DNA-cutting enzyme to destroy the X chromosome during the production of sperm, leading to predominantly male offspring, as females require two Xs. In their experiments, they managed to produce populations of the flies that were 80% male.
CRISPR may help curb malaria by altering a mosquito’s gut genes, new study suggests
16828Cornell Alliance for Science, Genetic Literacy Project, 2021-04-21 16:46:24.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife. The study is the latest in a series of steps toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Mosquito are becoming increasingly resistance to insecticides and malaria parasites are gaining resistance to antimalarial drugs, creating an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach to controlling mosquitoes, locusts and other insects. They work by creating genetically modified mosquitoes that, when released into the environment, mate with wild insects. The offspring contain genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite. But scientists must prove that this approach is safe and effective before releasing gene drive mosquitoes into the wild.
Fighting mosquitoes with mosquitoes
16825W. Feng, The Daily Targum, 2021-04-21 16:38:39.
When you think about the animal that has killed the greatest number of humans in the world, you generally tend to think of large predators. Is it perhaps the great white shark or maybe the cute but deadly hippopotamus? While these animals are certainly deadly, the number of annual fatalities caused by them are eclipsed by the number of individuals killed by the tiny blood-sucking mosquito. According to the World Health Organization, approximately 725,000 people are killed every year by mosquito-borne diseases. The mosquito has been the center of numerous pathogenic outbreaks over the last couple decades, such as the West Nile virus, malaria and the Zika virus. While conventional control strategies have been employed, these have all failed to stop the spread of these viruses. To combat this issue, one solution that has been proposed is gene drives. While further testing and research is still required to ensure the safety and efficacy of gene drives, the benefits of this technology far outweigh any potential consequences, lending them to be extremely helpful in the battle against insect-borne diseases.
CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues
17324R. Piergentili, A. Del Rio, F. Signore, F. U. Ronchi, E. Marinelli and S. Zaami, Cells, 10:24. 2021-04-21 12:06:42.
The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man. During the years this technique has been applied in several fields, such as agriculture for crop upgrade and breeding including the creation of allergy-free foods, for eradicating pests, for the improvement of animal breeds, in the industry of bio-fuels and it can even be used as a basis for a cell-based recording apparatus. Possible applications in human health include the making of new medicines through the creation of genetically modified organisms, the treatment of viral infections, the control of pathogens, applications in clinical diagnostics and the cure of human genetic diseases, either caused by somatic (e.g., cancer) or inherited (mendelian disorders) mutations. One of the most divisive, possible uses of this system is the modification of human embryos, for the purpose of preventing or curing a human being before birth. However, the technology in this field is evolving faster than regulations and several concerns are raised by its enormous yet controversial potential. In this scenario, appropriate laws need to be issued and ethical guidelines must be developed, in order to properly assess advantages as well as risks of this approach. In this review, we summarize the potential of these genome editing techniques and their applications in human embryo treatment. We will analyze CRISPR-Cas limitations and the possible genome damage caused in the treated embryo. Finally, we will discuss how all this impacts the law, ethics and common sense.
Eliminating malaria via a simple genetic modification
16822S. Gunn, Front Line Genomics, 2021-04-20 16:32:44.
Despite decades worth of research and efforts, data from 2015 onwards suggests that there has been no significant progress in reducing global malaria cases. Every year, around 400,00 people die from malaria, with over 90% of cases being within sub-Saharan Africa. The rise of mosquito resistance to pesticides as well as malaria parasite resistance to antimalarial drugs has emphasised the urgent need for the development of new tools to fight this disease. One approach that researchers are exploring is the use of gene drives. A gene drive is a genetic modification that can spread through a population at higher inheritance rates than normal. In this context, researchers can genetically modify mosquitos that, when released into the environment, would spread genes to either reduce mosquito populations or make them less likely to spread the malaria parasite. Due to concerns regarding the safety of gene drives, it is vital that researchers prove that this approach is safe and effective before releasing the modified mosquitos into the wild. There are currently no clear pathways for safely testing these tools within endemic countries.
This Malaria Preventing Mosquito Is Not A GMO But Is A Science Boost For Nature – Will Activists Want To Block It?
16816H. Campbell, science 2.0, 2021-04-20 16:13:03.
Mosquitoes like Aedes aegypti don't have any value ecologically. If Thanos snapped them out of existence tomorrow there is nothing they do that won't immediately be taken up by 3,000 other mosquito species, not to mention 25,000 bee species when it comes to pollination. The only thing they are great at is killing people; by being a leading source of vector-borne dengue disease. Not far behind is Anopheles gambiae mosquitoes, which carry malaria. Malaria kills nearly as many people each year as COVID-19 did in 2020 but there is no Warp Speed program to keep poor people in developing nations from dying. Environmental activists (overwhelmingly white and wealthy) instead spend $2 billion a year scaring people of color in other countries about science. Pesticides wiped out malaria in the U.S.(1) and remain the best way to go. DDT still works well and is in common use in afflicted countries.(2) Though banned politically in the U.S. half a century ago, our EPA literally writes the manual for how to spray it in homes elsewhere, but the Rachel Carson dream was to replace pesticides with genetically modified crops - optimizing nature to keep other parts of nature from killing everything using fewer chemicals.
Breeding Malaria Out: Scientists Engineer Mosquitos to Spread Antimalaria Genes
16800L. Papadopoulos, INTERSTING ENGINEERING, 2021-04-17 13:57:17.
According to the Centers for Disease Control and Prevention (CDC), malaria is a "serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans." There are four types of malaria parasites: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae with P. falciparum being the one most likely to result in death. But what if these mosquitos could be genetically altered to spread antimalaria genes instead of the disease? That would be nothing short of a miracle. Researchers from Imperial College London have successfully altered a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species. This innovation may result in curbing malaria once and for all. This is especially important as the parasite that causes malaria has been becoming increasingly resistant to antimalarial drugs.
Engineered sex ratio distortion by X-shredding in the global agricultural pest Ceratitis capitata
16837A. Meccariello, F. Krsticevic, R. Colonna, G. Del Corsano, B. Fasulo, P. A. Papathanos and N. Windbichler, BMC Biology, 19:78. 2021-04-16 14:29:21.
Genetic sex ratio distorters are systems aimed at effecting a bias in the reproductive sex ratio of a population and could be applied for the area-wide control of sexually reproducing insects that vector disease or disrupt agricultural production. One example of such a system leading to male bias is X-shredding, an approach that interferes with the transmission of the X-chromosome by inducing multiple DNA double-strand breaks during male meiosis. Endonucleases targeting the X-chromosome and whose activity is restricted to male gametogenesis have recently been pioneered as a means to engineer such traits.
Curbing Malaria’s Spread by Genetic Engineering
16792Anonymous, Genetic Engineering & Biotechnology News, 2021-04-15 13:03:49.
There is an urgent need to find new ways to combat the growing mosquito resistance to pesticides and malaria parasite resistance to antimalarial drugs. Gene drives are being tested as a new approach. In a new study, researchers from the Imperial College London reported that their approach brings gene drives one step closer as a potential strategy for eliminating malaria. Their study was published in the journal eLife, in a paper titled, “Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement.”
New genetic modification could cut malaria spread
16789Staff Writers, MALAYSIA NOW, 2021-04-15 12:56:54.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife on Tuesday. The study is the latest in a series of steps being taken toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Growing mosquito resistance to pesticides, as well as malaria parasite resistance to antimalarial drugs, has created an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach. They work by creating genetically modified mosquitoes that, when released into the environment, would spread genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite.
GeneConvene Global Collaborative Webinar Series | Ecological Relationships of Mosquito Disease Vectors: Anticipating Risk Assessment of Gene Drive Technologies
16713Stephanie James, Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2021-04-14 18:05:39.
An often-raised concern for the development of genetically modified mosquito technologies, particularly those involving gene drive, as tools to prevent disease transmission is the limitation of our understanding of the roles these species may play within the ecosystem. This series of webinars begins to explore what is known about the ecological relationships of mosquito vectors with regard to major types of species interactions. The speakers also will describe some of the methods by which potential interactions that may impact human or animal health and the environment can be examined in the context of case-by-case risk assessment and safety testing.
Ecological Relationships of Mosquito Disease Vectors: Anticipating Risk Assessment of Gene Drive Technologies
16707Stephanie James, Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2021-04-14 17:54:18.
An often-raised concern for the development of genetically modified mosquito technologies, particularly those involving gene drive, as tools to prevent disease transmission is the limitation of our understanding of the roles these species may play within the ecosystem. This series of webinars begins to explore what is known about the ecological relationships of mosquito vectors with regard to major types of species interactions. The speakers also will describe some of the methods by which potential interactions that may impact human or animal health and the environment can be examined in the context of case-by-case risk assessment and safety testing.
Researchers Using Mutant Mosquitoes To End Malaria, Which Kills 4 Lakh Per Year
16797M. Mohanti, India Times, 2021-04-14 13:20:52.
Every year, more than 22 crore people get infected with malaria and more than 4 lakh die because of it. In fact, in 2019, nearly half of the world's population was at risk of malaria. According to WHO, infants or children aged under 5 years are the most vulnerable group, accounting for two-third of all malaria deaths worldwide. Malaria is caused by parasites that are transmitted to people via the bites of infected female Anopheles mozzies. In a non-immune individual, symptoms--fever, headache, and chills--usually appear 10–15 days after the infective mosquito bite. If it goes untreated for a day, these mild symptoms can progress to severe illness, often leading to death, if bitten by the P. falciparum parasite.
Why do you think a gene drive approach could help with malaria and dengue?
16682Outreach Network for Gene Drive Research, 2021-04-12 14:42:36.
Why do you think a gene drive approach could help with malaria and dengue?
US Gene Drive Governance: A Special Feature in Health Security
16685L. Warmbrod, A. Kobokovich, R. West, G. K. Gronvall and M. Montague, Health Security, 19:131-132. 2021-04-08 14:51:20.
The novel potential of gene drives and related genetic pest control measures highlights a gap in the oversight of products using such technologies in the United States. The US Coordinated Framework for Regulation of Biotechnology, as applied by US Environmental Protection Agency, the US Food and Drug Administration, and US Department of Agriculture, may not fully encompass modern synthetic biology techniques that have significantly expanded the scope of genetic modification technology applications.
CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus
16674C. Quinn, A. Anthousi, C. Wondji and T. Nolan, bioRxiv, 2021.03.31.437891. 2021-03-31 13:57:08.
We describe herein an optimised transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in An. funestus.Competing Interest StatementThe authors have declared no competing interest.
Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa
16668J. B. Connolly, J. D. Mumford, S. Fuchs, G. Turner, C. Beech, A. R. North and A. Burt, Malaria Journal, 20:170. 2021-03-29 18:49:26.
Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus (dsxFCRISPRh) has recently been shown to increase rapidly in frequency in, and suppress, caged laboratory populations of the malaria mosquito vector Anopheles gambiae. Here, problem formulation, an initial step in environmental risk assessment (ERA), was performed for simulated field releases of the dsxFCRISPRh transgene in West Africa.
Experimenting with co-development: a qualitative study of gene drive research for malaria control in Mali
16639S. Hartley, K. Ledingham, R. Owen, S. Leonelli, S. Diarra and S. Diop, Social Science and Medicine, 2021-03-21 14:37:21.
Our findings suggest co-development is opening up previously expert-dominated spaces as researchers attempt to take responsibility for the societal implications of their work. However, its main function is as a project management tool to enable and instrumentally support technological development, field trials and eventual deployment. This function extends into areas which are traditionally the responsibility of the state, such as regulatory development, facilitated by Mali’s fragile political and economic situation. Paradoxically, co-development simultaneously depoliticises gene drive, masking power relations and closing down substantive debate and agency. Characterised by extreme poverty, conflict and weak institutions, Mali may become a site for technological experimentation where there is little interrogation of gene drive or its governance.
Ethics of Genome Editing
16622European Group on Ethics, European Group on Ethics in Science and New Technologies, 2021-03-19 18:16:09.
This Opinion addresses the profound ethical questions raised and revived by them. It analyses various domains of application, from human health to animal experimentation, from livestock breeding to crop variety and to gene drives. With its wide view across areas, it identifies underlying and overarching issues that deserve our concerted attention, among them, the different meanings that ought to be attributed to humanness, naturalness or diversity. This enables conclusions that provide panoramic perspectives complementing narrower, area-specific analyses. In the same vein, the Opinion is concerned with the global dimension of genome editing and its regulation and formulates recommendations with a particular focus on the international level.
Evaluating unintended consequences of intentional species introductions and eradications for improved conservation management
16631D. E. Pearson, T. J. Clark and P. G. Hahn, Conserv Biol, 2021-03-19 14:52:01.
We conducted a global literature review of these conservation actions to quantify how often unintended outcomes occur and to elucidate their underlying causes. We found that studies reported intended outcomes in 51% of cases, a combination of intended outcomes and unintended outcomes in 26% of cases, and strictly unintended outcomes in 10% of cases. Hence, unintended outcomes were reported in 36% of all cases evaluated. In evaluating overall conservations outcomes (weighing intended vs unintended effects), some unintended effects are fairly innocuous relative to successful conservation objectives whereas others result in serious unintended consequences in recipient communities. Importantly, we also found that studies that assessed a greater number of community interactions with the target species were more likely to report unintended outcomes, suggesting that unintended consequences may be under-reported due to insufficient vetting.
The ethical scientist in a time of uncertainty
16620L. Zoloth, Cell, 184:1430-1439. 2021-03-18 17:59:56.
Using the example of gene drives for malaria control to explore the problem of deep uncertainty in biomedical research, I argue that profound uncertainty is an essential feature. Applying the language and presumptions of the discipline of philosophical ethics, I describe three types of uncertainty that raise ethical challenges in scientific research. Rather than mitigate these challenges with excessive precautions and limits on progress, I suggest that researchers can cultivate classic values of veracity, courage, humility, and fidelity in their research allowing science to proceed ethically under conditions of deep uncertainty.
Driving to Safety: CRISPR-Based Genetic Approaches to Reducing Antibiotic Resistance
16614E. Bier and V. Nizet, Trends in Genetics, 2021-03-18 17:34:35.
The complex and challenging problem of reducing antibiotic resistance (AR) requires a network of both societal and science-based solutions to preserve the most lifesaving pharmaceutical intervention known to medicine. In addition to developing new classes of antibiotics, it is essential to safeguard the clinical efficacy of existing drugs. In this review, we examine the potential application of novel CRISPR-based genetic approaches to reducing AR in both environmental and clinical settings and prolonging the utility of vital antibiotics.
Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control
16629S. M. O'Loughlin, A. J. Forster, S. Fuchs, T. Dottorini, T. Nolan, A. Crisanti and A. Burt, G3-Genes Genomes Genetics, 2021-03-18 14:15:51.
Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were found across the alignment, with a maximum length of 164 bp. Length-corrected gene ontology analysis revealed that genes containing Anopheles ultra-conserved elements were over-represented in categories with structural or nucleotide binding functions. Known insect transcription factor binding sites were found in 48% of intergenic Anopheles ultra-conserved elements. When we looked at the genome sequences of 1142 wild-caught mosquitoes we found that 15% of the Anopheles ultra-conserved elements contained no polymorphisms. Our list of Anopheles ultra-conserved elements should provide a valuable starting point for the selection and testing of new targets for gene-drive modification in the mosquitoes that transmit malaria.
Meiotic Cas9 expression mediates genotype conversion in the male and female mouse germline.
16618A. J. Weitzel, H. A. Grunwald, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper, 2021.03.16.435716, 2021-03-17 17:52:21.
We previously showed that such a system of genotype conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double strand DNA break is feasible in the female mouse germline. In the male germline, however, all double strand breaks were instead repaired by end joining mechanisms to form an 'insertion/deletion' (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homology directed repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate genotype conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient double strand DNA break formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of genotype conversion and further increase the rate of 'super-Mendelian' inheritance from both male and female mice.Competing Interest StatementVMG, SMH, EB, and KLC hold advisory board positions with Synbal, Inc. All other authors declare that they have no competing interests.
Genetically Encoded CRISPR components Yield Efficient Gene Editing in the Invasive Pest, Drosophila suzukii
16602N. P. Kandul, E. J. Belikoff, J. Liu, A. Buchman, F. Li, A. Yamamoto, T. Yang, I. Shriner, M. J. Scott and O. Akbari, bioRxiv, 2021.03.15.435483. 2021-03-16 18:28:51.
Here we have developed transgenic strains that encode three different terminators and four different promoters to express Cas9 in both the soma and/or germline of SWD. The Cas9 lines were evaluated through genetic crossing to transgenic lines that encode single guide RNAs targeting the conserved X-linked yellow body and white eye genes. We find that several Cas9/gRNA lines display very high editing capacity. Going forward, these tools will be instrumental for evaluating gene function in SWD and may provide tools useful for the development of new genetic strategies for control of this invasive species.
Ugandan stakeholder hopes and concerns about gene drive mosquitoes for malaria control: new directions for gene drive risk governance
16600S. Hartley, R. D. J. Smith, A. Kokotovich, C. Opesen, T. Habtewold, K. Ledingham, B. Raymond and C. B. Rwabukwali, Malaria Journal, 20:149. 2021-03-16 18:12:21.
The African Union’s High-Level Panel on Emerging Technologies identified gene drive mosquitoes as a priority technology for malaria elimination. The first field trials are expected in 5–10 years in Uganda, Mali or Burkina Faso. In preparation, regional and international actors are developing risk governance guidelines which will delineate the framework for identifying and evaluating risks. Scientists and bioethicists have called for African stakeholder involvement in these developments, arguing the knowledge and perspectives of those people living in malaria-afflicted countries is currently missing. However, few African stakeholders have been involved to date, leaving a knowledge gap about the local social-cultural as well as ecological context in which gene drive mosquitoes will be tested and deployed. This study investigates and analyses Ugandan stakeholders’ hopes and concerns about gene drive mosquitoes for malaria control and explores the new directions needed for risk governance.
Current Effector and Gene-Drive Developments to Engineer Arbovirus-Resistant Aedes aegypti (Diptera: Culicidae) for a Sustainable Population Replacement Strategy in the Field
16596W. R. Reid, K. E. Olson and A. W. E. Franz, J Med Entomol, 2021-03-12 20:35:28.
Conventional mosquito control efforts based on insecticide treatments and/or the use of bednets and window curtains are currently insufficient to reduce arbovirus prevalence in affected regions. Novel, genetic strategies that are being developed involve the genetic manipulation of mosquitoes for population reduction and population replacement purposes. Population replacement aims at replacing arbovirus-susceptible wild-type mosquitoes in a target region with those that carry a laboratory-engineered antiviral effector to interrupt arboviral transmission in the field.
Gene Drives Built to Follow More Stringent Rules of the Road
16590Anonymous, Genetic Engineering & Biotechnology News, 2021-03-08 19:57:32.
Gene drives, or systems that accelerate the spread of desirable genetic traits into a population, may be built to achieve specific levels of spread when released into the wild. By exerting control over the degree of spread, those who unleash gene drives may realize the benefits promised by gene drives—the suppression of disease-carrying or crop-destroying insects—while minimizing the risks that unintended genetic changes could occur that would lead to undesirable ecological outcomes. A gene drive engineered to allow for a high degree of control was recently introduced by scientists based at the University of California, San Diego (UCSD). The new gene drive is a “split drive” system. Details appeared in an article titled, “Inherently confinable split-drive systems in Drosophila.” The article demonstrates that split-drive systems may allow various genetic parameters and strategies to be used to either limit or extend drive potential.
Gene-Editing Approach To Control the Invasive Gray Squirrel
16572M. Campbell, Technology Networks, 2021-03-08 14:33:09.
Biodiversity refers to the extent of the variety of life that is found on planet Earth – and it is currently under threat. Changes in biodiversity have been flagged as "surpassing safe limits" for several years, and world leaders and scientists across the globe are consequently exploring different ways to address the crisis. Invasive species, defined by National Geographic as "an organism that is not indigenous, or native, to a particular area", threaten planet Earth's biodiversity to an even greater extent than climate change. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) Global Assessment Report found that the number of invasive species per country have risen by ~70% since 1970 across 21 countries that were included in the report. An example of an invasive species is the gray squirrel Sciurus carolinensis found in the UK, which outcompetes the native red squirrel for resources and habitats and carries diseases that are not pathogenic to themselves but can kill red squirrels.
New gene-drive technologies can help control crop pests
16569Anonymous, AZO Life Sciences, 2021-03-08 14:21:28.
The supposed gene drives, which exploit CRISPR technology to affect genetic inheritance, show the potential to quickly spread particular genetic traits across the populations of a specified species. For instance, gene-drive technologies used on insects are being developed to stop the spread of devastating diseases, like dengue and malaria, by inhibiting mosquito hosts from becoming infected. Gene-drives are being designed in agricultural fields to help regulate or remove economically damaging crop pests. But together with the potential to modify populations, there have been concerns about the long-term impacts of these transformative novel technologies in the wild. Both scientists and ethicists have queried about how the so-called gene drives, once turned loose in a regional population, can be controlled if required. Scientists from the University of California San Diego (UC San Diego), Tata Institute for Genetics and Society (TIGS) at UC San Diego, and their collaborators at UC Berkeley have now designed a new technique that gives more control over the release of gene drives. Information about the new “split drive” was published in the Nature Communications and eLife journals on March 5th, 2021.
Experts’ moral views on gene drive technologies: a qualitative interview study
16565N. de Graeff, K. R. Jongsma and A. L. Bredenoord, BMC Medical Ethics, 22:25. 2021-03-08 13:56:59.
Gene drive technologies (GDTs) promote the rapid spread of a particular genetic element within a population of non-human organisms. Potential applications of GDTs include the control of insect vectors, invasive species and agricultural pests. Whether, and if so, under what conditions, GDTs should be deployed is hotly debated. Although broad stances in this debate have been described, the convictions that inform the moral views of the experts shaping these technologies and related policies have not been examined in depth in the academic literature.
Eliminating Mosquitoes with Precision Guided Sterile Males
16563M. Li, T. Yang, M. Bui, S. Gamez, T. Wise, N. P. Kandul, J. Liu, L. Alcantara, H. Lee, J. R. Edula, R. Raban, Y. Zhan, Y. Wang, N. DeBeaubien, J. Chen, H. M. Sanchez C, J. B. Bennett, I. Antoshechkin, C. Montell, J. M. Marshall and O. S. Akbari, bioRxiv, 2021.03.05.434167. 2021-03-06 20:07:26.
Here we develop a molecular genetic control system termed precision guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and eliminate mosquitoes in multigenerational population cages. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.
New ‘Split-drive’ System Puts Scientists in the (Gene) Driver Seat
16555M. Aguilera, UC San Diego News Center, 2021-03-05 19:42:37.
Gene-drive technologies applied in insects, for example, are being designed to halt the spread of devastating diseases such as malaria and dengue by preventing mosquito hosts from becoming infected. In agricultural fields, gene-drives are being developed to help control or eliminate economically damaging crop pests. But along with the capacity to alter populations, concerns have been raised regarding the long-term effects of these transformative new technologies in the wild. Researchers and ethicists have voiced questions about how gene drives, once turned loose in a regional population, could be held in check if necessary. Now, researchers at the University of California San Diego, Tata Institute for Genetics and Society (TIGS) at UC San Diego and their colleagues at UC Berkeley have developed a new method that provides more control over gene drive releases. Details of the new “split drive” are published March 5 in the journals Nature Communications and eLife.
In Uganda, genetically modified mosquitoes bring hope and fear
16550Anonymous, africanews, 2021-03-05 19:32:29.
Scientists here are investigating whether populations of the malaria-carrying insects can be reduced by genetic modification. They're looking at the viability of releasing large numbers of genetically modified mosquitos into the wild to influence future generations. The study is being led by scientists here at the institute in Kampala with researchers from the Target Malaria group. Dr. Jonathan Kayondo is the principal investigator managing the project. He says the disease can be deadly for children, especially those under five-years-old. "The aim here is to develop a new vector control tool for the suppression of malaria transmission," says Dr. Jonathan Kayondo.
A confinable home and rescue gene drive for population modification
16579N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. S. Akbari, eLife, 10:e65939. 2021-03-05 16:30:16.
Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification Home-and-Rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal, and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy.
Renew Europe | The science & ethics of gene drive technology from a conservation & development perspective
16584Renew Europe, Renew Europe, 2021-03-05 15:18:26.
This hearing intends to examine gene-drive technology and its possible impacts, including unintended ones and reveal the complexity of an unknown technology with inherent uncertainties. Scientists from different backgrounds in the field of gene-drive research will present most recent scientific findings and allow us to exchange on a technical, but also ethical debate. Hosted by MEPs Soraya Rodríguez & Charles Goerens with a keynote speech by Commissioner for Envinronment Virginijus Sinkevičius.
Ecology: Gene drives may help control invasive grey squirrel in the UK
16557A. Korn, EurekaAlert, 2021-03-04 19:50:50.
Gene drives introduce genes into a population that have been changed to induce infertility in females, allowing for the control of population size. However, they face technical challenges, such as controlling the spread of altered genes as gene drive individuals mate with wild individuals, and the development of genetic resistance, which may render the gene drive ineffective. To address these challenges, Nicky Faber and colleagues used computer modelling to investigate the effectiveness of a combination of three gene drive technologies using the grey squirrel as a case study.
Genetically modified mosquitoes for better health
16527D. Devis, COSMOS, 2021-03-04 18:24:41.
One method of preventing these mosquito-born diseases is to use insecticides to kill the mozzies and remove them, but sometimes this only works as a short term solution, or has unintended devasting effects on the ecosystem. Another method for decreasing the number of disease-carrying mozzies is to introduce disease resistant, genetically modified mozzies. These transgenic mozzies could be part of a gene drive system where they have a newly introduced disease-resistant gene, linked up with CRISPR mechanisms that help the gene dominate in the population by continuing to copy itself through the genome. All of this requires very thorough risk assessment.
Genetically modified squirrels could curb growing population of greys
16542S. Knapton, Telegraph, 2021-03-04 16:06:59.
Mutant grey squirrels, genetically modified to spread infertility genes, could be released into the wild to tackle the burgeoning population,
Expert reaction to a paper suggesting that gene drives could be used to help control grey squirrel numbers in the UK
16540Anonymous, Science Media Centre, 2021-03-04 15:59:10.
This study assesses the prospects for using a gene drive to control invasive grey squirrels in the UK. This is a modelling study exploring the potential for such an approach – no such gene drives currently exist and developing them for grey squirrels would be quite a long-term project. Invasive species are a major problem for biodiversity and conservation; in many cases there are no adequate methods for control. Genetic methods may provide new options, potentially both more effective and with fewer off-target effects. Most work on gene drives has focused on mosquitoes; this study is unusual in focusing on a vertebrate (grey squirrel), though there has also been interest in targeting invasive populations of mice and rats on islands.
CRISPR gene drives may come to a squirrel near you.
16536Anonymous, NewsBeezer, 2021-03-04 15:48:43.
Today’s gene drive technologies could be blended to provide control of the invasive gray squirrel population in the UK – with minimal risk to other populations, according to a new modeling published in the journal Scientific reports. Gene driving introduces altered genes into a population that can cause infertility in women. This allows scientists to control the size of the population. However, this tactic faces technical difficulties such as controlling the spread of altered genes while certain animals that are part of the gene drive population mate with uncontrolled populations ̵
Quantifying the risk of vector-borne disease transmission attributable to genetically modified vectors
16530G. R. Hosack, A. Ickowicz and K. R. Hayes, Royal Society Open Science, 8:201525. 2021-03-03 18:28:51.
The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of Anopheles coluzzii carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.
Developing GDi-CRISPR System for Multi-copy Integration in Saccharomyces cerevisiae
16544Z.-X. Zhang, Y.-Z. Wang, Y.-S. Xu, X.-M. Sun and H. Huang, Applied Biochemistry and Biotechnology, 2021-03-03 16:12:03.
This study aims to develop a low-cost and easy-to-use multi-copy integration tool in S. cerevisiae. Firstly, twenty-one Cas proteins from different microorganisms were tested in S. cerevisiae to find the functional Cas proteins with optimal cleavage ability. Results showed that eight Cas proteins can complete gene editing. However, most of the transformants have low copy numbers, which may be caused by high cutting efficiency exceeding the repair rate. Therefore, the effect of donor translocation order was further investigated. Results showed that 4 copies were obtained by donor first translocation. Then, the gene drive delta site integration system by the CRISPR system (GDi-CRISPR) was developed by combining gene drive principle and CRISPR system. To be clear, the gRNA was put into donor fragments. Then, both of them were integrated into the genome, which can drive further cutting and repair due to increasing number of gRNA. Instead of high-throughput screening or resistance pressure, 6 copies were obtained in only 5–6 days using the GDi-CRISPR system. It is expected to further advance the development of S. cerevisiae multi-copy integration tools.
How Brussels can help or hinder the fight against malaria
16511F. Okumu, EURACTIV, 2021-03-01 21:46:44.
In the wake of the pandemic, the world has much for which to thank Europe. Not only did European science lead the field in developing the first approved vaccine against COVID-19, but the EU’s long history of rigorous regulatory approval has also allowed for public confidence in its safety and efficacy. For years, the EU has provided the global gold standard for protecting human health and safety while fostering scientific innovation to improve lives and wellbeing. Heading into a crucial decade for world preservation, the EU has another chance to unleash the power of science in the search for solutions to existential challenges both at home and in neighbouring regions.
Demographic and psychographic drivers of public acceptance of novel invasive pest control technologies
17086F. Eppink, P. J. Walsh and E. MacDonald, Ecology and Society, 26. 2021-03-01 15:15:26.
Invasive mammals are a primary threat to New Zealand's endemic species. In remote areas, aerial delivery of poison is the preferred method of pest management, although it faces some public backlash. Novel pest control technologies are currently being investigated as alternatives but may face similar concerns. To investigate potential social and demographic determinants of public perceptions of new methods for pest control, we conducted a national choice experiment, focused on several novel technologies: gene drives, Trojan females, and species-specific poisons. We found that preferences strongly depend on the type of technology, with Trojan female technology strictly preferred to the other two. Although several characteristics affected preferences in predictable ways education, trust in science, and liberal political leaning increased acceptance ;the same did not hold with preferences for aerial delivery. Our results are useful for targeting future engagement campaigns and leveraging existing efforts.
Designing gene drives to limit spillover to non-target populations
16516G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim, PLOS Genetics, 17:e1009278. 2021-02-25 15:02:27.
We develop mathematical models of gene-drive dynamics that incorporate migration between a target and non-target populations to investigate the possibility of effectively applying a gene drive in the target population while limiting its spillovers to the non-target population (‘differential targeting’). We observe that the feasibility of differential targeting depends on the gene-drive design specification, as well as on the migration rates between the populations. Even when differential targeting is possible, as migration increases, the possibility for differential targeting disappears. We find that differential targeting can be effective for low migration rates, and that it is sensitive to the design of the gene drive under high migration rates. We suggest that differential targeting could be used, in combination with other mitigation measures, as an additional safeguard to limit gene drive spillovers.
GeneConvene Global Collaborative Webinar Series | Ecological Modeling in Risk Assessment of Gene Drives
16445Hector Quemada and David O'Brochta, 2021-02-23 18:20:53.
Unlike non-gene drive organisms, which can be limited in time and space and therefore provide data in small scale tests that can be relevant to large scale releases, the potential for large-scale spread from a limited release, even in well-isolated trials, means that reliance on models will be a more important tool for risk assessors. To date, this work has only started to receive attention. This series of four presentations deals with the development and use of models in ecology generally. Some of these presentations will also deal with the use of models specifically to assess the ecological impacts of gene drive organisms.
GeneConvene Webinar Series on: Ecological Modeling in Risk Assessment of Gene Drives
16435Hector Quemada and David O'Brochta, 2021-02-23 16:59:25.
Unlike non-gene drive organisms, which can be limited in time and space and therefore provide data in small scale tests that can be relevant to large scale releases, the potential for large-scale spread from a limited release, even in well-isolated trials, means that reliance on models will be a more important tool for risk assessors. To date, this work has only started to receive attention. This series of four presentations deals with the development and use of models in ecology generally. Some of these presentations will also deal with the use of models specifically to assess the ecological impacts of gene drive organisms.
Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive
16657K. P. Oh, A. B. Shiels, L. Shiels, D. V. Blondel, K. J. Campbell, J. R. Saah, A. L. Lloyd, P. Q. Thomas, F. Gould, Z. Abdo, J. R. Godwin and A. J. Piaggio, Evolutionary Applications, 2021-02-22 17:41:41.
Here we used pooled whole-genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications.
Modeling impact and cost-effectiveness of gene drives for malaria elimination in the Democratic Republic of the Congo
16477N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, medRxiv, 2020.06.29.20142760. 2021-02-22 13:51:04.
Using a spatially explicit, agent-based model of malaria transmission in eight representative provinces of the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that include existing interventions such as insecticide-treated nets and case management of symptomatic malaria. Gene drive mosquitoes could eliminate malaria and were the most cost-effective intervention overall if the drive component was highly effective with at least 95% X-shredding and associated cost of deployment below 7.17 $int per person per year. Suppression gene drive could be a cost-effective supplemental intervention for malaria elimination, but tight constraints on drive effectiveness and cost ceilings may limit its feasibility.
Split versions of Cleave and Rescue selfish genetic elements for measured self limiting gene drive
16426G. Oberhofer, T. Ivy and B. A. Hay, PLoS genetics, 17:e1009385. 2021-02-18 20:00:28.
Self-sustaining Cleave and Rescue (ClvR) elements include a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene, a tightly linked recoded version of the essential gene resistant to cleavage (the Rescue), and a Cargo. ClvR spreads by creating loss-of-function (LOF) conditions in which those without ClvR die because they lack functional copies of the essential gene. We use modeling to show that when the Rescue-Cargo and one or both components required for LOF allele creation (Cas9 and gRNA) reside at different locations (split ClvR), drive of Rescue-Cargo is self-limiting due to a progressive decrease in Cas9 frequency, and thus opportunities for creation of LOF alleles, as spread occurs. Importantly, drive strength and duration can be extended in a measured manner-which is still self-limiting-by moving the two components close enough to each other that they experience some degree of linkage. With linkage, Cas9 transiently experiences drive by hitchhiking with Rescue-Cargo until linkage disequilibrium between the two disappears, a function of recombination frequency and number of generations, creating a novel point of control. We implement split ClvR in Drosophila, with key elements on different chromosomes. Cargo/Rescue/gRNAs spreads to high frequency in a Cas9-dependent manner, while the frequency of Cas9 decreases.
Plain language summary: How do we have a public conversation about new technologies for conservation? The possibilities and pitfalls of scientific language
16409Annonymous, Relational Thinking, 2021-02-17 18:30:27.
Having caused a catastrophic decline of animal species, people now look to new technologies to reverse the damage. Gene drive is a potential tool that could increase the proportion of male offspring in rat populations and eventually reduce their overall numbers. Some suggest this tool could eliminate rats from islands, like New Zealand, where rats have a devastating impact on native species. While holding much potential, the New Zealand public has shown hesitation towards genetic tools. In our study, we investigated how four articles, each emphasizing a different aspect of gene drive (i.e., humaneness, pragmatism, decision making, and scientific innovation), impacted opinion towards gene drive alongside people’s emotional responses, biases, and perceived risks towards the tool.
Scientifically framed gene drive communication perceived as credible but riskier
16406E. A. MacDonald, E. D. Edwards, J. Balanovic and F. Medvecky, People and Nature, 2021-02-17 18:23:29.
Framing is a communication technique in which certain beliefs or values are emphasized that resonate with the target audience. Framing may increase how much people objectively think about new information and update their opinions; framing may mitigate emo
Detailed genome map of malaria vector
16381The Hindu, Aspirant World, 2021-02-14 15:03:12.
In order to engineer advanced forms of defence against malaria transmission, including targeted CRISPR and gene drive–based strategies, scientists require intricate knowledge of the genomes of vector mosquitoes. CRISPR technology is a gene-editing tool which allows researchers to easily alter DNA sequences and modify gene function.They produced a new reference genome for the Asian malaria vector mosquito Anopheles stephensi.
Researchers Unveil Detailed Genome of Invasive Malaria Mosquito
16374M. Aguilera, UC San Diego News Center, 2021-02-11 20:37:12.
Mosquito-transmitted malaria remains the number one worldwide killer among vector-borne diseases, claiming more than 400,000 human lives in 2019. In order to engineer advanced forms of defense against malaria transmission, including targeted CRISPR and gene drive-based strategies, scientists require intricate knowledge of the genomes of vector mosquitoes. Mahul Chakraborty—a project scientist at the University of California, Irvine, working with colleagues at the Tata Institute for Genetics and Society (TIGS) at UC San Diego and India, and the Institute of Bioinformatics and Applied Biotechnology in Bangalore, India—has produced a groundbreaking new reference genome for the Asian malaria vector mosquito Anopheles stephensi. Full details of the genome, which the scientists say is now on par with the best animal genomes available to science (humans and fruit flies), are published in the journal BMC Biology.
Optimized CRISPR tools and site-directed transgenesis in Culex quinquefasciatus mosquitoes for gene drive development
16372X. Feng, V. Lopez Del Amo, E. Mameli, M. Lee, A. L. Bishop, N. Perrimon and V. M. Gantz, bioRxiv, 2021.02.10.430702. 2021-02-11 20:33:00.
Here, we developed a Culex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in both Culex and Drosophila and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.
Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly
16376M. Chakraborty, A. Ramaiah, A. Adolfi, P. Halas, B. Kaduskar, L. T. Ngo, S. Jayaprasad, K. Paul, S. Whadgar, S. Srinivasan, S. Subramani, E. Bier, A. A. James and J. J. Emerson, BMC Biology, 19:28. 2021-02-10 20:40:13.
The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.
Projects to target a range of pest control solutions
16366K. McCormack, The Chronicle, 2021-02-10 20:19:28.
With the annual national cost of established vertebrate pest animals estimated to be around $800 million, and over $4 billion for weeds, it’s in Australia’s best interest to try and tackle these pesky problems at their root causes. 19 projects will be funded following a competitive grant process to research and advance breakthrough solutions to control some of Australia’s worst established pest animals and weeds, including fall armyworm and prickly acacia. Minister for Agriculture, Drought and Emergency Management, David Littleproud, said he was delighted with the high calibre and diversity of projects coming from the popular grant round.
A Code of Ethics for Gene Drive Research
16379G. J. Annas, C. L. Beisel, K. Clement, A. Crisanti, S. Francis, M. Galardini, R. Galizi, J. Grünewald, G. Immobile, A. S. Khalil, R. Müller, V. Pattanayak, K. Petri, L. Paul, L. Pinello, A. Simoni, C. Taxiarchi and J. K. Joung, The CRISPR Journal, 4:19:1-8. 2021-02-10 14:57:13.
A code of ethics can be a useful tool for all parties involved in the development and regulation of gene drives and can be used to help ensure that a balanced analysis of risks, benefits, and values is taken into consideration for the interest of society and humanity. We have developed a code of ethics for gene drive research with the hope that this code will encourage the development of an international framework that includes ethical guidance of gene drive research and is incorporated into scientific practice by gaining broad agreement and adherence.
Assisting Evolution: How Far Should We Go to Help Species Adapt?
16369E. Kolbert, YaleEnvironment360, 2021-02-09 20:28:55.
It was a hot, intensely blue day in the Australian Outback, about 350 miles north of Adelaide. I was tagging along with Moseby as she checked the batteries on the motion-sensitive cameras that dot Arid Recovery, an ecosystem restoration project she and her husband launched in 1997. The project sprawls over 47 square miles of red earth and scrub. It’s entirely surrounded by a six-foot-tall fence, which is designed to keep out feral cats and foxes. Inside the main fence is a series of smaller fenced-in paddocks. Several years ago, Moseby decided to start adding cats into some of these. Her reasoning was simple and, in its own way, radical. The outback ecosystem had been so fundamentally changed, that, if the native animals were to survive, they would have to change, too. Perhaps they could be trained to avoid cats, which were introduced to the country by the British colonists and now can be found virtually everywhere in Australia, including most islands.
Should we dim the sun? Will we even have a choice
16384E. Klein, New York Times, 2021-02-09 15:06:18.
“Under a White Sky” is going to be on my best books of 2021 list. It’s a wonderful work. Kolbert is the Pulitzer Prize-winning author of “The Sixth Extinction,” which you may have read. She is a staff writer at The New Yorker and just one of the great science journalists of this time, and particularly one of the great climate journalists of this age. But this book, this book’s existence is evidence of how badly that fight is going. This is a book about what we are going to need to contemplate in the coming years that we don’t want to. It’s a book about taking responsibility for how irreversibly we have altered the natural world; how often we have tried to control it, and then watched those attempts at control fail; how often the best most scientific minds of the age have come up with some brilliant solution, implemented it, and then watched calamity result. And at the same time — and this is what makes the book so worthwhile — it is a book about how there is no going back. Not now, not ever. We are in the Anthropocene. The future from here is an endless layering on of new efforts to control the consequences of our past efforts. We don’t get to flinch or pretend we don’t have to contemplate any of this. We’ve gone too far. One of the hardest things to do as a writer — and I tell you this from personal experience — is to write ambivalence. It’s easy to write a polemic or a sharp take. It is hard to write down the middle path, where you are simply describing things as they are, knowing that every possible obvious answer you can come to is probably a bad one, knowing that the hubris embedded in past attempts to solve this problem means any future brilliant idea is likely to end that way, too, but that doesn’t mean we can do nothing. But Kolbert walks that path really beautifully here, which is why I wanted to talk to her for the show. As always, my email is [email protected]. I’m always interested to know who you’d like to see on the show. The weirder, the better. So send me your guest suggestions. Here’s Elizabeth Kolbert.
Public attitudes towards synthetic biology
16363CSIRO, Synthetic Biology Future Science Platform, 2021-02-08 20:06:39.
A national survey has been conducted by CSIRO’s Synthetic Biology Future Science Platform as an important first step in measuring public attitudes towards synthetic biology. The survey draws on the views of more than 8,000 Australians, and researchers are examining the data to determine current attitudes to these emerging technologies
In Our Image: The Ethics of CRISPR Genome Editing
16272J. C. Eissenberg, Biomolecular Concepts, 12:1-7. 2021-02-06 16:55:38.
Here, I discuss the ethics surrounding the transformative CRISPR/Cas9mediated genome editing technology in the contexts of human genome editing to eradicate genetic disease and of gene drive technology to eradicate animal vectors of human disease.
Grey squirrels: is birth control the solution to Britain’s invasive species problem?
16275J. Gilchrist, The Conversation, 2021-02-03 17:03:29.
As with the UK’s other invasive species, such as rabbits, signal crayfish and Japanese knotweed, introducing the grey squirrel has proved to be an expensive mistake. Not only do grey squirrels displace red squirrels, they strip bark from trees. A recent report estimated that this could cost commercial forestry and native woodlands £1.1 billion (US$1.5 billion) over the next 40 years, including revenue lost to damaged timber, reduced carbon storage, tree replacement costs and squirrel control. Despite efforts to kill grey squirrels over several decades, their populations remain large and widespread.
Mosquitoes genetically modified to be resistant to Zika
16259Staff, Lab+Life Scientist, 2021-02-02 15:55:50.
Researchers have wrestled with different strategies for controlling the spread of Zika virus, which is transmitted to humans from female mosquito bites. One approach, which has been approved by the US Environmental Protection Agency, will see more than 750 million genetically modified mosquitoes released into the Florida Keys in 2021 and 2022. These ‘suicide mosquitoes’ are genetically altered to produce offspring that die before emerging into adults and therefore cannot bite humans and spread disease.
Experts oppose plan to breed mosquitoes
16279T. Abet, Daily Monitor, 2021-02-01 17:11:29.
Environmentalists have opposed the plan to breed and release genetically modified mosquitoes in the country to curb malaria prevalence. They say the act presents substantial human and environmental health risks. Their objection follows last week’s announcement by scientists at Uganda Virus Research Institute (UVRI) that they have embarked on a series of activities aimed at breeding and releasing genetically modified mosquitoes (GMMs) that could curb malaria transmission.
Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance
16290A. Hammond, X. Karlsson, I. Morianou, K. Kyrou, A. Beaghton, M. Gribble, N. Kranjc, R. Galizi, A. Burt, A. Crisanti and T. Nolan, PLOS Genetics, 17:e1009321. 2021-01-29 21:53:25.
Here we show that restricting the cutting activity of the gene drive to the germline tissue is crucial to maintaining its potency and we illustrate how failure to restrict this activity can lead to the generation of mutations that can make mosquitoes resistant to the gene drive.
Les Européens très critiques vis-à-vis du forçage génétique
16231L. Duboua-Lorsch, EURACTIV, 2021-01-29 16:38:41.
Cette technique, qui vise à éradiquer ou modifier certaines espèces dites nuisibles, sera au cœur des négociations cette année, alors que se profile la COP15 sur la biodiversité. maginez un monde débarrassé d’insectes porteurs de maladies, de parasites agricoles, d’espèces envahissantes… Les possibilités semblent infinies avec la nouvelle technique du « gene drive », en français forçage génétique. Née au début des années 2000, cette technique de modification génétique permet à un gène d’être transmis de manière quasi-systématique à ses descendants. En quelques générations seulement, l’ensemble d’une espèce sauvage peut être remplacée par ces nouveaux individus génétiquement forcés.
Genetically modified mosquitoes to curb malaria
16221T. Abet, Daily Monitor, 2021-01-29 16:20:15.
Scientists at Uganda Virus Research Institute (UVRI) have started breeding mosquitoes with the aim of modifying their genetic materials and releasing them to the environment to curb malaria transmission. The genetically modified mosquitoes, according to the scientists, do not transmit malaria parasites when they bite. Dr Jonathan Kayondo, the project lead coordinator at the UVRI, said when the modified male mosquito mates with common mosquitoes, the female off springs are infertile. This, he explained will significantly suppress the population or eliminate mosquitoes thereby stopping malaria transmission and deaths.
New genetically modified mosquitoes to help fight malaria
16216D. Zirimala, Capital Radio FM, 2021-01-29 16:11:15.
According to Dr. Jonathan Kayondo, the principal investigator of the Target Malaria project, the genetically modified mosquitoes do not transmit malaria parasites when they bite. These are made infertile so that when they cross breed with the female anopheles mosquito, they are not able to reproduce. He says with this new research project, they are complimenting the already existing malaria control methods such as insecticides treated mosquito nets, indoor residual spraying and drugs but there is need to get additional tools to help eradicate the disease.
Proceedings of an expert workshop on community agreement for gene drive research in Africa – Co-organised by KEMRI, PAMCA and Target Malaria [version 1; peer review: awaiting peer review]
16224D. Thizy, L. Pare Toe, C. Mbogo, D. Matoke-Muhia, V. P. Alibu, S. K. Barnhill-Dilling, T. Chantler, G. Chongwe, J. Delborne, L. Kapiriri, E. Nassonko Kavuma, S. Koloi-Keaikitse, A. Kormos, K. Littler, D. Lwetoijera, R. Vargas de Moraes, N. Mumba, L. Muten, Gates Open Research, 2021-01-28 16:25:31.
Target Malaria, the Kenya Medical Research Institute and the Pan African Mosquito Control Association co-organised a workshop with researchers and practitioners on this topic to question the model proposed by Target Malaria in its research so far that involved the release of genetically modified sterile male mosquitoes and how this could be adapted to future studies involving gene drive mosquito releases for them to offer reflections about potential best practices. This paper shares the outcomes of that workshop and highlights the remaining topics for discussion before a comprehensive model can be design
GENE DRIVE ACCEPTANCE SURVEY
16233YouGov, Pollinis, 2021-01-27 16:47:37.
This representative survey was conducted by the international market research institute YouGov and polled 8.826 citizens from 8 EU countries in December 2020. It was commissioned by WeMove Europe, Save Our Seeds (Germany), Skiftet (Sweden), France Nature Environnement (FNE) (France), POLLINIS (France), OGM Dangers (France), Bund für Umwelt und Naturschutz (BUND) (Germany), Deutscher Naturschutzring (DNR) (Germany), Umweltinstitut München (Germany), Za Zemiata (Bulgaria). Deviations from 100% are due to rounding.
Demographic feedbacks can hamper the spatial spread of a gene drive
16203L. Girardin and F. Débarre, arXiv, 2021-01-27 15:32:53.
Our results indicate that taking into account the interplay between population dynamics and population genetics might actually be crucial, as it can effectively reverse the direction of the invasion and lead to failure. Our findings can be extended to other bistable systems, such as the spread of cytoplasmic incompatibilities caused by Wolbachia.
Genetically-modified mosquitoes key to stopping Zika virus spread
16208University of Missouri, Medical Xpress, 2021-01-26 13:52:44.
Alexander Franz, an associate professor in the MU College of Veterinary Medicine, collaborated with researchers at Colorado State University by using CRISPR gene-editing technology to produce mosquitoes that are unable to replicate Zika virus and therefore cannot infect a human through biting. "We genetically manipulated these mosquitoes by inserting an artificial gene into their genome that triggers one of the immune pathways in the midgut to recognize and destroy the RNA genome of Zika virus," Franz said. "By developing these mosquitoes that are resistant to the virus, the disease cycle is interrupted so transmission to humans can no longer take place." Franz added that the genetic modification is inheritable, so future generations of the altered mosquitoes would be resistant to Zika virus as well.
Anopheles gambiae Genome Conservation as a Resource for Rational Gene Drive Target Site Selection
16102N. Kranjc, A. Crisanti, T. Nolan and F. Bernardini, Insects, 12. 2021-01-23 14:46:16.
In this study we describe a bioinformatic pipeline that allows the analysis of whole genome data for the identification of highly conserved regions that can point at potential functional or structural constraints. The analysis was conducted across the genomes of 22 insect species separated by more than hundred million years of evolution and includes the observed genomic variation within field caught samples of Anopheles gambiae and Anopheles coluzzii, the two most dominant malaria vectors. This study offers insight into the level of conservation at a genome-wide scale as well as at per base-pair resolution.
Drivers of mosquito mating
16110N. C. Manoukis, Science, 371:340. 2021-01-22 15:54:49.
Gene drive systems are based on the release of organisms whose genomes have been modified or engineered to spread a desired allele or trait (such as resistance to the parasites that cause malaria) through a population. Success will depend on the release of genetically modified males that will be able to mate with wild females. Beyond gene drive strategies, in mosquitoes it is understood that only males can be released as part of any genetic pest control (GPC) program (7); females feed on blood to lay eggs, and releasing insects that will feed on humans is widely unacceptable.
Clock genes and environmental cues coordinate Anopheles pheromone synthesis, swarming, and mating
16108G. Wang, J. Vega-Rodríguez, A. Diabate, J. Liu, C. Cui, C. Nignan, L. Dong, F. Li, C. O. Ouedrago, A. M. Bandaogo, P. S. Sawadogo, H. Maiga, T. L. Alves e Silva, T. V. Pascini, S. Wang and M. Jacobs-Lorena, Science, 371:411. 2021-01-22 15:35:30.
Knockdown of per and tim expression affects Anopheles gambiae s.s. and Anopheles stephensi male mating in the laboratory, and it reduces male An. coluzzii swarming and mating under semifield conditions. Light and temperature affect mosquito mating, possibly by modulating per and/or tim expression. Moreover, the desaturase gene desat1 is up-regulated and rhythmically expressed in the heads of swarming males and regulates the production of cuticular hydrocarbons, including heptacosane, which stimulates mating activity.
The Promises and Realities of Integration in Synthetic Biology: A View From Social Science
16287L. Carter and A. Mankad, Frontiers in Bioengineering and Biotechnology, 8. 2021-01-21 17:25:32.
We take stock of thepromises and realities of science integration by sharing our experiences of embarking onthis very challenge in Australia. We conclude by offering suggestions for bringing aboutthe enabling conditions for improved integration across the natural and social sciences.Four key actions are articulated to help pivot synthetic biology toward a more integratedscientific endeavor: (a) formalizing inclusivity from inception to project conclusion; (b)valuing differing philosophical positions as a strength rather than a barrier; (c) acceptingthat integration takes persistence and communication but is immensely rewarding; and(d) promoting meaningful interactions, such as pursuing joint opportunities, co-designingand co-publishing research. We argue that these actions arekey enablers for realizingscience integration in synthetic biology.
Co‐developing a common glossary with stakeholders for engagement on new genetic approaches for malaria control in a local African setting
16104E. Chemonges Wanyama, B. Dicko, L. Pare Toe, M. B. Coulibaly, N. Barry, K. Bayala Traore, A. Diabate, M. Drabo, J. K. Kayondo, S. Kekele, S. Kodio, A. D. Ky, R. R. Linga, E. Magala, W. I. Meda, S. Mukwaya, A. Namukwaya, B. Robinson, H. Samoura, K. Sanogo, Malaria Journal, 20:53. 2021-01-21 14:51:47.
Scientific terminologies are mainly lacking in local languages, yet when research activities involve international partnership, the question of technical jargon and its translation is crucial for effective and meaningful communication with stakeholders. Target Malaria, a not-for-profit research consortium developing innovative genetic approaches to malaria vector control, carried out a linguistic exercise in Mali, Burkina Faso and Uganda to establish the appropriate translation of its key terminology to local languages of sites where the teams operate.
Exploring Gene Drive Technologies in Agriculture, Biodiversity and Human Disease
15963The GBIRd Partnership and The GeneConvene Global Collaborative, Gene Drive Research Forum, 2021-01-14 21:37:12.
The GBIRd Partnership and The GeneConvene Global Collaborative recently collaborated through The Gene Drive Research Forum, to create and produce an engaging conversation between Drs. Fred Gould and Charles Godfray about gene drive technologies – the potential benefits and complicating factors for agriculture, biodiversity, and human disease.
Responsibly Developing Gene Drives: The GeneConvene Global Collaborative
15969J. Toomey, Bill of Health, 2021-01-13 19:18:06.
The GeneConvene Global Collaborative, a project of the Foundation for the National Institutes of Health, was started this past July to promote the responsible development and regulation of gene drive technologies. It brings together researchers, regulators and stakeholders around the world to develop best practices for gene drive research and implementation. Because of my prior writing on this topic, I participated in GeneConvene’s fall webinar series and spoke with scientists there about the project. Debates about the regulation of gene drives are unique in several respects, because the technology is unique in several respects.
‘Clever Approach’: Scientists Create GM-Free Organisms Using Genetic Engineering
15955A. Paleja, The WIRE, 2021-01-11 17:07:06.
Farther to the north, researchers at the University of Minnesota have developed a novel way to resolve this problem. They used genetic engineering to create organisms for release that are not genetically modified. Maciej Maselko was a postdoctoral associate at the university when he was part of the study. “Slow and expensive regulatory approvals for GM insect release” inspired the team’s work, he told The Wire Science. “We looked for a way to get the benefits achieved with GM insect release but without needing to release GM insects.” He conceptualised the experiment with PhD scholar Siba Das and molecular biology professor Michael Smanski. The results were published in November 2020. In a typical control intervention, researchers release sterile male mosquitoes into the environment. These compete with wild males to mate with wild females. Mosquitoes mate only once in their lifetime. Since mating with sterile mosquitoes produces no offspring, the local mosquito population begins to fall. The methods to select these male mosquitoes to subsequently release are either labour intensive or need specialised equipment. The colony that scientists rear is also often three times larger than the number of males released. Third, a mosquito lives typically for 8-10 days. So scientists must select the males to release close to the site of intervention.
CRISPR and the splice to survive: New gene-editing technology could be used to save species from extinction—or to eliminate them.
16011E. Kolbert, New Yorker, 2021-01-11 14:25:59.
About a year ago, not long before the pandemic began, I paid a visit to the center, which is an hour southwest of Melbourne. The draw was an experiment on a species of giant toad known familiarly as the cane toad. The toad was introduced to Australia as an agent of pest control, but it promptly got out of control itself, producing an ecological disaster. Researchers at the A.C.D.P. were hoping to put the toad back in the bottle, as it were, using crispr.
Double drives and private alleles for localised population genetic control
15945K. Willis and A. Burt, bioRxiv, 2021.01.08.425856. 2021-01-09 16:30:16.
In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of PAM sites in island and mainland populations of the malaria mosquito Anopheles gambiae indicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.
Self-Deleting Genes Project To Tackle Mosquito-Borne Diseases
15923D. Ozdemir, INTERESTING ENGINEERING, 2021-01-08 18:58:57.
Did you know that mosquitoes kill at least 725,000 persons every year? They truly are one of the world's deadliest animals which is the reason why scientists from all around are trying to find new ways of dealing with them. Controlling mosquito populations and preventing them from transmitting disease at times through genetic engineering is one way of doing that. Now, a new Texas A&M AgriLife Research project has plans of enabling "test runs" of the proposed changes in mosquitoes that are automatically deleted from their genetic code. Researchers have used genetic engineering in the past to modify mosquitoes in a way that they pass on infertility, don't grow wings, can't spread malaria, or have impaired smell. However, as New Atlas reports, this sort of modification can have harmful consequences that may be impossible to reverse when released into the wild.
Targeting evolutionary conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus
15943M. Walter, R. Perrone and E. Verdin, bioRxiv, 2021.01.08.425902. 2021-01-08 16:26:29.
Here, we analyze in cell culture experiments the evolution of resistance in a gene drive against human cytomegalovirus. We report that after an initial invasion of the wildtype population, a drive-resistant population is positively selected over time and outcompetes gene drive viruses. However, we show that targeting evolutionary conserved regions ensures that drive-resistant viruses have a replication defect, leading to a long-term reduction of viral levels. This marks an important step toward developing effective gene drives in viruses, especially for therapeutic applications.
Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles
15938J. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer, Mol Ecol, 2021-01-07 19:32:54.
Using spatially explicit simulations, we show that the release of a suppression drive can result in what we term "chasing" dynamics, in which wild-type individuals recolonize areas where the drive locally eliminated the population. Despite the drive subsequently reconquering these areas, complete population suppression often fails to occur or is substantially delayed. This increases the likelihood that the drive is lost or that resistance evolves. We analyze how chasing dynamics are influenced by the type of drive, its efficiency, fitness costs, and ecological factors such as the maximal growth rate of the population and levels of dispersal and inbreeding. We find that chasing is more common for lower efficiency drives when dispersal is low and that some drive mechanisms are substantially more prone to chasing behavior than others. Our results demonstrate that the population dynamics of suppression gene drives are determined by a complex interplay of genetic and ecological factors, highlighting the need for realistic spatial modeling to predict the outcome of drive releases in natural populations.
Demystifying the Risk Assessment Process for Laboratory-Based Experiments Utilizing Invasive Genetic Elements: It Is More Than Gene Drive
18156Z. N. Adelman, Applied Biosafety, 2021-01-07 18:05:08.
Advances in recombinant DNA approaches have resulted in the development of transgene architectures that severely bias their own inheritance, a process commonly referred to as ?gene drive.? The rapid pace of development, combined with the complexity of many gene drive approaches, threatens to overwhelm those responsible for ensuring its safe use in the laboratory, as even identifying that a specific transgene is capable of gene drive may not be intuitive. Although currently gene drive experiments have been limited to just a few species (mosquitoes, flies, mice, and yeast), the range of organisms used in gene drive research is expected to increase substantially in the coming years. Here the defining features of different gene drive approaches are discussed. Although this will start with a focus on identifying when gene drive could or could not occur, the emphasis will also be on establishing risk profiles based on anticipated level of invasiveness and persistence of transgenes in the surrounding environment. Attention is also called to the fact that transgenes can be considered invasive without being considered gene drive (and vice versa). This further supports the notion that adequate risk assessment requires information regarding the specific circumstances a given transgene or set of transgenes is capable of invading a corresponding population. Finally, challenges in the review and evaluation of work involving gene drive organisms are discussed.
Next-generation tools to control biting midge populations and reduce pathogen transmission
15940P. Shults, L. W. Cohnstaedt, Z. N. Adelman and C. Brelsfoard, Parasites and Vectors, 14:31. 2021-01-07 14:52:23.
Biting midges of the genus Culicoides transmit disease-causing agents resulting in a significant economic impact on livestock industries in many parts of the world. Localized control efforts, such as removal of larval habitat or pesticide application, can be logistically difficult, expensive and ineffective if not instituted and maintained properly. With these limitations, a population-level approach to the management of Culicoides midges should be investigated as a means to replace or supplement existing control strategies. Next-generation control methods such as Wolbachia- and genetic-based population suppression and replacement are being investigated in several vector species. Here we assess the feasibility and applicability of these approaches for use against biting midges. We also discuss the technical and logistical hurdles needing to be addressed for each method to be successful, as well as emphasize the importance of addressing community engagement and involving stakeholders in the investigation and development of these approaches.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
ARS Science Key to Stopping ‘Man-Eating’ Parasite
15973S. Elliott, Tellus, 2021-01-04 19:30:15.
Screwworm infestations were once prevalent in the United States, with 230,000 cases reported in 1935 alone. ARS scientists Edward Knipling and Raymond Bushland conceived and developed the sterile insect technique (SIT) to control and eradicate screwworms. With SIT, sterilized male blow flies were released to breed with wild flies. Since female blow flies mate only once, the coupling effectively removed that female and her potential offspring from the population.
Conservation pest control with new technologies: public perceptions
15913E. A. MacDonald, M. B. Neff, E. Edwards, F. Medvecky and J. Balanovic, Journal of the Royal Society of New Zealand, 2021-01-04 13:45:38.
We conducted eleven focus groups in New Zealand to explore three questions about novel technologies (gene drive and two others for comparison of pest control tools): (1) what are the risks/benefits? (2) how do they compare to current methods? and (3) who should be represented on a panel that evaluates the tools and what factors should they consider?
The New Yorker Magazine: Gene Drives as a Tool for Saving Nature
16277E. Heber, Island Conservation, 2021-01-03 17:07:04.
In a recent New Yorker Magazine article, entitled “CRISPR and the Splice to Survive,” journalist and best-selling author Elizabeth Kolbert dives into the world of gene drive research. She touches on aspects of gene drive research from altering the toxin produced by cane toads to recovering nearly-extinct trees to eradicating invasive mice through attrition, all to understand the possibilities this tool could hold.
Edit, undo: Temporary gene editing could help solve the mosquito problem
15900L. Dormehl, digitaltrends, 2020-12-31 14:22:29.
But if SyFy original movies have taught us anything, it’s that genetically tweaking organisms and then releasing them can… well, not go quite according to plan.With that in mind, a new Texas A&M AgriLife Research project seeks to test out genetic modifications of mosquitos that would delete themselves from the genetic code after a certain period. This means that “test runs” of genetic changes could be made, knowing that everything will reset to normal after a designated period like one year (which equates to around 20 generations of mosquito).
Self-deleting genes promise risk-free genetic engineering of mosquitoes
15852D. Quick, New Atlas, 2020-12-29 18:53:49.
A new project by Texas A&M AgriLife Research is looking to enable "test runs" of genetic changes to mosquitoes that are automatically deleted. Various angles of attack using genetic engineering to combat mosquitoes have been pursued in recent years, including modifying them so they pass on infertility, don't grow wings, can't spread malaria or have impaired smell. But making genetic modifications to an organism and then releasing them into the wild runs the risk of unintended and harmful consequences that may be difficult to reverse. That's where the new Texas A&M AgriLife Research project comes in. It is looking to enable "test runs" of genetic modifications that would then automatically be deleted from the mosquitoes' genetic code after a period of time.
Self-deleting genes to be tested as part of mosquito population control concept
15926B. Hays, UPI, 2020-12-28 18:59:14.
Scientists at Texas A&M have developed a new technique for altering the genes of mosquitoes -- the new technology will cause genetic changes to self-delete from the mosquitoes' genome. Thanks to the breakthrough, described Monday in the Philosophical Transactions of the Royal Society B, researchers can now test-run experimental gene edits without permanently altering a mosquito's genome."People are wary of transgenes spreading in the environment in an uncontrolled manner. We feel that ours is a strategy to potentially prevent that from happening," Zach Adelman, professor of entomology at the Texas A&M College of Agriculture, said in a news release. "The idea is, can we program a transgene to remove itself? Then, the gene won't persist in the environment."
$3.9M project on self-deleting genes takes aim at mosquito-borne diseases
15847O. Kuchment, AGRILIFE Today, 2020-12-28 18:52:03.
To control mosquito populations and prevent them from transmitting diseases such as malaria, many researchers are pursuing strategies in mosquito genetic engineering. A new Texas A&M AgriLife Research project aims to enable temporary “test runs” of proposed genetic changes in mosquitoes, after which the changes remove themselves from the mosquitoes’ genetic code. The project’s first results were published on Dec. 28 in Philosophical Transactions of the Royal Society B, titled “Making gene drive biodegradable.”
Self-deleting genes tested as part of the concept of mosquito population control
15844charlottelarson, NEWYORK NEWS TIMES, 2020-12-28 18:49:28.
Most genetic engineering strategies designed to control mosquito populations, and their ability to spread diseases such as malaria, require gene editing to be combined with gene drives. Gene drives allow altered DNA to spread rapidly throughout the population.
Genetic pest management and the background genetics of release strains
15695P. T. Leftwich, L. G. Spurgin, T. Harvey-Samuel, C. J. E. Thomas, L. C. Paladino, M. P. Edgington and L. Alphey, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190805. 2020-12-28 15:35:20.
We discuss issues around strain selection and the potential consequences of such introgression. We conclude that such introgression is probably harmless in almost all circumstances, and could, in theory, provide specific additional benefits to the release programme. We outline population monitoring approaches that could be used, going forward, to determine how background genetics may affect GPM. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
Control of malaria-transmitting mosquitoes using gene drives
15693T. Nolan, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190803. 2020-12-28 15:31:23.
In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
Making gene drive biodegradable
15687J. Zapletal, N. Najmitabrizi, M. Erraguntla, M. A. Lawley, K. M. Myles and Z. N. Adelman, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190804. 2020-12-28 15:02:10.
Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation.
Vector dynamics influence spatially imperfect genetic interventions against disease
16547M. K. Yuksel, C. H. Remien, B. Karki, J. J. Bull and S. M. Krone, Evolution, Medicine, and Public Health, 9:1-10. 2020-12-27 16:20:40.
In spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside unprotected areas and into areas that block its reproduction. Here, we consider the sensitivity of this process to biological details: do simple generalities emerge that may facilitate interventions?We develop formal mathematical models of this process similar to standard Ross–Macdonald models, but (i) specifying spatial structure of two patches, with vector transmission blocked in one patch but not in the other, (ii) allowing temporary human movement (travel instead of migration) and (iii) considering two different modes of mosquito biting.We find that there is no invariant effect of disrupting spatial structure with travel.
Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors
15898A. Kormos, G. C. Lanzaro, E. Bier, G. Dimopoulos, J. M. Marshall, J. Pinto, A. Aguiar dos Santos, A. Bacar, H. Sousa Pontes Sacramento Rompão and A. A. James, The American Journal of Tropical Medicine and Hygiene, 2020-12-21 14:17:29.
Although guidelines and recommendations for engagement for gene drives have recently been described, we argue here that communities and stakeholders should lead the planning, development, and implementation phases of engagement. The RBM provides a new approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs.
New GE unintentionally leaves traces in cells
15620C. Then, Testbiotech, 2020-12-18 16:22:58.
A new scientific publication shows that CRISPR/Cas gene scissor applications in animals unintentionally leave traces. The findings are not related to unintended changes in the DNA, which have often been described, but to gene regulation, i.e. epigenetics. The effects are heritable and may, for example, result in disruption of embryonic development. The new scientific publication describes CRISPR/Cas experiments with mice in which their DNA is cut and additional genetic information inserted. Besides intended changes in DNA in the target region, the findings also showed unintended changes in so-called epigenetic markers that control gene regulation. The effects were heritable and could still be identified after ten generations. According to the authors, the effects can also be used to identify CRISPR/Cas gene scissor applications.
Converting female mosquitoes to non-biting males with implications for mosquito control
15614M. V. Candy, Vet Candy, 2020-12-18 15:57:05.
Virginia Tech researchers have proven that a single gene can convert female Aedes aegypti mosquitoes into fertile male mosquitoes and identified a gene needed for male mosquito flight. Male mosquitoes do not bite and are unable to transmit pathogens to humans. Female mosquitoes, on the other hand, are able to bite. Female Aedes aegypti mosquitoes require blood to produce eggs, making them the prime carriers of the pathogens that cause Zika and dengue fever in humans. "The presence of a male-determining locus (M locus) establishes the male sex in Aedes aegypti and the M locus is only inherited by the male offspring, much like the human Y chromosome," said Zhijian Tu, a professor in the Department of Biochemistry in the College of Agriculture and Life Sciences. "By inserting Nix, a previously discovered male-determining gene in the M locus of Aedes aegypti, into a chromosomal region that can be inherited by females, we showed that Nix alone was sufficient to convert females to fertile males. This may have implications for developing future mosquito control techniques." These findings were published in the Proceedings of the National Academy of Sciences.
New insect species made via genetic engineering
15610L. Leffer, SCIENCELINE, 2020-12-18 15:47:16.
A biotech fast-forward button for evolution is on the horizon. Researchers say they have used a novel genetic engineering method to create several new species of fruit fly in the lab for the first time — an achievement which might help put a future without malaria and other insect-borne diseases within reach. The approach, called synthetic speciation, could prove useful in creating safer pest-control technologies, says Maciej Maselko, a postdoctoral fellow studying synthetic biology at Macquarie University. In one far-off scenario, according to Maselko, synthetic speciation might even be applied to generate designer organisms that could pollinate plants or even detect landmines. Maselko and his team published their findings September 8 in Nature Communications. “Speciation has occurred billions of times on the planet, but hasn’t been engineerable [before],” says Michael Smanski, a molecular biologist at the University of Minnesota and member of the research team. Maselko, Smanski and their colleagues have previously used a similar method to engineer “species like” differences in yeast in 2018, but their more recent results are the first time the concept has been proven possible in a multicellular animal. This method could produce untold numbers of new animal varieties within months rather than millennia, Smanski says.
Core commitments for field trials of gene drive organisms
15161K. C. Long, L. Alphey, G. J. Annas, C. S. Bloss, K. J. Campbell, J. Champer, C.-H. Chen, A. Choudhary, G. M. Church, J. P. Collins, K. L. Cooper, J. A. Delborne, O. R. Edwards, C. I. Emerson, K. Esvelt, S. W. Evans, R. M. Friedman, V. M. Gantz, F. Gould,, Science, 370:1417-1419. 2020-12-17 20:01:12.
While field trials of gene drive organisms (GDOs) ultimately will depend on public policy decisions, those engaged in GDO work can play critical roles in support of these decisions by generating evidence and developing evaluation strategies in fair and effective partnerships with relevant authorities and other stakeholders. The authorship of this statement reflects the current reality that GDO development is occurring primarily in high-income countries. However, fair partnership with counterparts and communities in low- and middle-income countries where many GDOs have the highest potential for positive impact, as well as recognition of the need for capacity-building and global cooperation, underlies each of our commitments.
Scientists paved the way for field trials of gene-driven organisms
15559K. Winslet, FLORIDA News Times, 2020-12-17 15:01:59.
The recent rise of gene drive research, accelerated by CRISPR-Cas9 gene editing technology, has brought about a wave of transformation throughout science.Developed with selected traits that have been genetically engineered to spread throughout the population, Gene Drive Organisms (GDOs) provide solutions to a variety of difficult health and environmental challenges, from control to protection of dengue and malaria. A crop against plant pests that has the power to dramatically change the way it develops.But before these gene-drive organisms move from laboratory to field testing, scientists are proposing courses for responsible testing of this powerful technology. These issues are addressed in the new Policy Forum article on Biotechnology Governance, “Core Commitment for Field Trials of Gene Drive Organisms,” published December 18, 2020. Science By more than 40 researchers, including several scientists at the University of California, San Diego.“Gene drives have led to rapid research, so we need to take a step back and think about its application and its impact on humankind,” said Akbari, the lead author of the article. Associate Professor, Faculty of Biological Sciences, University of California, San Diego. “A new initiative to tackle field testing is to ensure that testing is conducted safely, transparent, publicly accountable, and scientifically, politically and socially robust.”
Technical Support to Burkina Faso on Gene Drive Stage 2 Dossier Review
15557AUDA-NEPAD, AUDA-NEPAD, 2020-12-17 14:58:32.
AUDA-NEPAD in partnership with the National Biosafety Agency (ANB) in Burkina Faso organised a training workshop to support to the National Biosafety Committee (NBC) on stage 2 dossier review, on December 3 – 5, 2020, in Bobo-Dioulasso, Burkina Faso. In addition to the NBC members, and based on recommendations from previous in-country consultations, the meeting audience was extended to include researchers, faculty members and PhD students. The meeting brought together 25 participants. Amongst the countries piloting the gene drive research in the continent, Burkina Faso has successfully completed the activities in stage 1 of the process nd is now contemplating to commence stage 2. An application has been prepared and submitted to the national regulatory agency, following a successful pre-review by the Institutional Biosafety Committee (IBC).
Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance
15554Y. Devos, M. B. Bonsall, L. G. Firbank, J. Mumford, F. Nogué and E. A. Wimmer, Trends in Biotechnology, 2020-12-17 14:48:35.
Risk assessors, risk managers, developers, potential applicants, and other stakeholders at many levels discuss the need for new or further risk assessment guidance for deliberate environmental releases of gene drive-modified organisms. However, preparing useful and practical guidance entails challenges, to which we offer recommendations based on our experience drafting guidance.
Scientists Set a Path for Field Trials of Gene Drive Organisms
15551M. Aguilera, UC San Diego News Center, 2020-12-17 14:41:55.
The modern rise of gene drive research, accelerated by CRISPR-Cas9 gene editing technology, has led to transformational waves rippling across science. Gene drive organisms (GDOs), developed with select traits that are genetically engineered to spread through a population, have the power to dramatically alter the way society develops solutions to a range of daunting health and environmental challenges, from controlling dengue fever and malaria to protecting crops against plant pests. But before these gene drive organisms move from the laboratory to testing in the field, scientists are proposing a course for responsible testing of this powerful technology. These issues are addressed in a new Policy Forum article on biotechnology governance, “Core commitments for field trials of gene drive organisms,” published Dec. 18, 2020 in Science by more than 40 researchers, including several University of California San Diego scientists.
A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias
15480S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey, bioRxiv, 2020.12.15.421271. 2020-12-16 14:45:08.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. Additionally, by making use of the tight linkage of white to the sex-determining locus, we were able to elucidate mechanisms of inheritance bias. We find inheritance bias through homing in double heterozygous males, but find that a previous report of the same drive occurred through meiotic drive. We propose that other previously reported 'homing'design gene drives may in fact bias their inheritance through other mechanisms with important implications for gene drive design.Competing Interest StatementThe authors have declared no competing interest.
Evading resistance to gene drives
15422R. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020.08.27.270611. 2020-12-12 15:44:15.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered sequentially) would allow arbitrary levels of suppression. The most favorable case for evolution of resistance appears to be with suppression homing drives in which resistance is dominant and fully suppresses transmission distortion; partial suppression by resistance heterozygotes or recessive resistance are less prone to resistance evolution. Given that it is now possible to engineer CRISPR-based gene drives capable of circumventing allelic resistance, this design may allow for the engineering of suppression gene drives that are effectively resistance-proof.
Interdisciplinary development of a standardized introduction to gene drives for lay audiences
15381C. E. Schairer, C. Triplett, A. Buchman, O. S. Akbari and C. S. Bloss, BMC Medical Research Methodology, 20:15. 2020-12-10 15:09:37.
While there is wide consensus that the public should be consulted about emerging technology early in development, it is difficult to elicit public opinion about innovations unfamiliar to lay audiences. We sought public input on a program of research on genetic engineering to control mosquito vectors of disease that is led by scientists at the University of California and funded by the U.S. Defense Advanced Research Projects Agency (DARPA). In preparation for this effort, we developed a series of narrated slideshows to prompt responses to the development of gene drive mosquito control strategies among lay people. We describe the development and content of these slideshows and evaluate their ability to elicit discussions among focus group participants.
A Gene Drive Could Wipe Out Mosquitoes. But What If We Want To Turn It Off?
15424A. Winkler, freethink, 2020-12-05 15:48:03.
Gene drives are powerful tools: they allow scientists to hack how animals pass down genes to their offspring. They could allow us to wipe out malaria-carrying mosquitoes, preserve endangered species, or fight off crop-eating pests. But once it's out in the wild, a gene drive can't be stopped from spreading — and that makes people nervous. If there are unintended consequences, we want to be able to pull the brakes. Now, UC San Diego researchers have developed a new genetic system that would let scientists halt or neutralize gene drives, even after they are released into the wild. The implications could be huge.
Targeting female flight for genetic control of mosquitoes
15310D. Navarro-Payá, I. Flis, M. A. E. Anderson, P. Hawes, M. Li, O. S. Akbari, S. Basu and L. Alphey, PLOS Neglected Tropical Diseases, 14:e0008876. 2020-12-03 20:11:01.
The yellow fever mosquito and the Southern house mosquito are important vectors of infectious diseases. Given their widespread presence across tropical and subtropical regions of the world and the increased risk of spread due to global warming there is a growing need for population control. Gene drives aim to spread a genetic element within target genes required for mosquito reproduction to disrupt their function and crash a population. Female-specific genes provide interesting candidates for population control since female mosquitoes determine the reproductive capacity of a population as well as being the actual vectors of disease. Here we describe a study on Actin-4 loss in both Aedes aegypti and Culex quinquefasciatus, where we observe female-specific disruption of flight ability and propose it as a candidate for genetic methods of population suppression.
Evaluating Gene Drive Approaches for Public Benefit
15296M. R. Santos, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:14:49.
Gene drive approaches—those which bias inheritance of a genetic element in a population of sexually reproducing organisms—have the potential to provide important public benefits. The spread of selected genetic elements in wild populations of organisms may help address certain challenges, such as transmission of vector-borne human and animal diseases and biodiversity loss due to invasive animals. Adapting various naturally occurring gene drive mechanisms to these aims is a long-standing research area, and recent advances in genetics have made engineering gene drive systems significantly more technically feasible. Gene drive approaches would act through changes in natural environments, thus robust methods to evaluate potential research and use are important.
Engineered Gene Drives and their Value in the Control of Vector-Borne Diseases, Weeds, Pests, and Invasive Species
15294K. Hefferon and R. Herring, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:10:55.
Genetic engineering has created potential for moving medical and agricultural research and application frontiers forward in unprecedented ways. Despite its accepted use as a powerful tool in medical research, genetic modification and genome editing technologies remain controversial in large-scale ecological intervention and open-field agriculture. Gene drive is a technology based on genome editing that enables a trait to be pushed through a given population at a greater than expected rate. While gene drives show enormous promise as a way to address a number of challenges, such as the reduction of populations of disease-spreading pests and invasive species, they also incite great social unease because of unknown risks. The following chapter describes the mechanics of gene drives and how they could be utilized to control vector-borne diseases, weeds, and crop pests and even protect populations of endangered species. Limitations and risks associated with gene drive technologies, such as containment strategies and potential resistance, are discussed. Finally, the social impacts of gene drives with respect to international governance and public acceptance are considered.
Engineered Gene Drives: Ecological, Environmental, and Societal Concerns
15292J. Kuzma, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:07:26.
This chapter overviews the types, purposes, and potential impacts of gene drive organisms (GDOs) and discusses challenges with foreseeing and assessing these impacts prior to their environmental release. It concludes with a few examples of risk analysis methods and governance systems that scholars have proposed to cope with the novelty of GDOs and uncertainties associated with their use. With GDOs poised for release in the near future, it is urgent that technologists, ecologists, social scientists, ethicists, stakeholders, and publics work together to grapple with the immense challenges associated with assessments of GDOs and the design of governance systems to ensure their responsible development and potential use.
Genetically Engineered Fish: Potential Impacts on Aquaculture, Biodiversity, and the Environment
15290R. A. Dunham and B. Su, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:03:48.
Studies on transgenic fish for the aquaculture industry have focused on improving growth rates, enhancing disease resistance, altering body composition, acting as biological factories for medical proteins, and even altering temperature tolerance and coloration. The future impact of transgenesis will likely be quite large. Growth hormone-transgenic salmon has been approved for human consumption and has been introduced to the market in Canada and soon to the USA. This is the first human consumption of approved transgenic meat. Transgene insertion has many pleiotropic effects. Several studies have projected the fitness of transgenic fish to be low, in general, compared to non-transgenic and wild fish; thus, their environmental risk is likely low and they would have minimal, if any, long-term impact on ecosystems or biodiversity. However, there have been no actual escapements; thus, only projections of risk are available based on small-scale experiments and the characteristics of transgenic fish compared to controls. An active area of research is repressible transgenic sterilization and sterilization using gene editing, both of which would allow application of transgenic fish with only short-term consequences for ecosystems in the worst-case scenario. Transgenic technology could also be potentially used to reduce or eliminate populations of nuisance species.
Invasive Species Control and Resolution of Wildlife Damage Conflicts: A Framework for Chemical and Genetically Based Management Methods
15286L. Clark, J. Eisemann, J. Godwin, K. E. Horak, K. Oh, J. O’Hare, A. Piaggio, K. Pepin and E. Ruell, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 16:52:40.
Vertebrate wildlife damage management relates to developing and employing methods to mitigate against damage caused by wildlife in the areas of food production, property damage, and animal or human health and safety. Of the many management tools available
GMOs: Implications for Biodiversity Conservation and Ecological Processes
15283Chaurasia, Anurag , Hawksworth, David L., Pessoa de Miranda, Manoela., GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 16:45:05.
This book covers a broad spectrum of topics related to GMOs and allied new gene-based technologies, biodiversity, and ecosystem processes, bringing together the contributions of researchers and regulators from around the world. The aim is to offer a clear view of the benefits and effects of genetically modified crops, insects, and other animals on the soil microbiome and ecological processes. Contributors examine issues related to the development of risk assessment procedures and regulations designed to maximize benefits while minimizing risks. Beyond the scientific challenges of GMOs, the book explores the broad and contentious terrain of ethical considerations. The contributors discuss such questions as the unintended, possibly unforeseen, consequences of releasing GMOs into ecosystems, and the likelihood that the full effects of GMOs could take years, even decades, of close monitoring to become evident. The importance of developing a precautionary approach is stressed.
Reply to: “Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported”
15264C. Souto-Maior, J. G. King, L. M. Sartori, R. Maciel-de-Freitas and M. G. M. Gomes, Nature Communications, 11:6113. 2020-11-30 19:09:46.
Ant et al.4 claim that concerns with the data and broader analysis make our conclusions misleading. We herein respond to their comments by demonstrating the robustness of our results to different treatments of the data, and expand our arguments for replacing currently adopted methods by those introduced in our paper.
Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported
15258T. H. Ant, M.-V. Mancini, J. Martinez and S. P. Sinkins, Nature Communications, 11:6111. 2020-11-30 18:48:33.
King et al.3 used DENV infection and transmission modelling to reinterpret experimental data from two previous studies4,5. The authors claimed that wMel Wolbachia increase the mean susceptibility of Ae. aegypti to DENV, contradicting various other studies6,7,8,9,10,11,12. Here, we raise concerns with the experimental approaches used to generate one of the primary datasets on which the modelling is based, and we discuss how these limitations could make some of the original conclusions misleading.
Mosquito population modification: the drive to malaria eradication
15272A. A. James, BugBitten BMC, 2020-11-27 14:37:56.
We have had considerable success in the past demonstrating that we can use modern molecular biological and insect transgenesis tools to make genes that prevent mosquitoes from passing on parasites (see 1 and 2). We have focused most recently on laboratory experiments to find ways to move these genes into wild mosquito populations.
Split drive killer-rescue provides a novel threshold-dependent gene drive
15254M. P. Edgington, T. Harvey-Samuel and L. Alphey, Scientific Reports, 10. 2020-11-25 18:32:01.
Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given that real-world components inevitably have such imperfections. We show that although end-joining repair mechanisms may cause the system to break down, under certain conditions, it should persist over time scales relevant for genetic control programs. The potential of such a system to provide localised population suppression via sex ratio distortion or female-specific lethality is also explored. Additionally, we investigate the effect on introduction thresholds of adding an extra CRISPR base element, showing that this may either increase or decrease dependent on parameter context
Transformation and slippage in co-production ambitions for global technology development: The case of gene drive
16634K. Ledingham and S. Hartley, Environmental Science & Policy, 116:78-85. 2020-11-24 17:41:43.
Co-production is an increasingly popular framework for knowledge generation, evaluation and decision making. Despite its potential to open up decisions and practices to the input of others, co-production regularly falls short of its transformative ambitions. Through documentary analysis, we investigate the meaning and dynamics of co-production as it stretches beyond the local into global research and technology spaces. We find that in the case of global gene drive, the meaning of co-production is extended in novel ways and underpinned by new possibilities for meaningful transformation. At the same time, we also identify a simultaneous resurfacing of reductive framings of collaboration. In the paper we present ‘slippage’ as a useful heuristic in helping to understand why co-production fails. We argue that if co-production in these new spaces is to achieve its transformative ambitions, there is a need to engage with new and entrenched knowledge hierarchies that contribute to this slippage.
FNIH Panel on Gene Drive Regulation Emphasizes Need for Local Community Engagement
15222C. Rizk, GenomeWeb, 2020-11-19 21:16:21.
Genetically modified organisms are another topic of deep debate, with some activists agitating for and getting governments to implement deep restrictions on modified crops. More recently, GMO crops have started to regain public favor, particularly in countries where boosting the levels of nutrients in staple crops could provide a benefit for children, or where certain genome modifications could increase crop yields. But reversing public biases and, more importantly, governmental regulations against GMOs won't be a simple matter, even if scientists can show a benefit to the modifications. So, when it comes to the development of the gene drive — another gene modification technology meant to promote the spread of certain genes in organisms such as mosquitoes in order to control or eradicate their populations in a controlled manner — many researchers are determined to foster debate that focuses on the science, includes local communities in the discussion, and leads to governance and regulations that will benefit both the environment and human health.
‘A plague to be reckoned with’: UMN research creates a buzz with invasive fruit fly research
15238B. Most, The Minnesota Daily, 2020-11-18 13:26:31.
n early November, assistant professor Mike Smanski published an article about a new breakthrough in this research, demonstrating for the first time this kind of genetic engineering was possible in the common fruit fly. This shows that researchers could engineer this work into spotted wing drosophila in the future. The University’s Smanski Lab has also studied this technique in mosquitoes, zebra fish and carp, but never with this type of fruit fly, he said. “These are all a new class of genetic pesticide, basically, that allow you to engineer the pest organism itself and convert that pest organism into the pesticide,” Smanski said. Through this work the researchers can create a pest that is biologically the same, but when the females mate with these genetically modified males, they will not produce viable offspring, he said. This sterile insect technique can be helpful not only in reducing the population of insects, but in reducing the impacts of insecticides on surrounding species and nearby ecosystems, said Feltman, a second-year biochemistry, molecular biology and biophysics graduate student.
Engineering biological diversity: the international governance of synthetic biology, gene drives, and de-extinction for conservation
15251J. L. Reynolds, Current Opinion in Environmental Sustainability, 49:1-6. 2020-11-17 18:23:24.
In the face of insufficient progress in conserving and restoring biodiversity, the in situ use of advanced genetic modification, gene drives, and other biotechnologies for conservation purposes are being considered, researched, and developed. This paper introduces the methods, applications, environmental risks, and social challenges of ‘conservationist synthetic biology’; reviews existing governance, with an emphasis on international instruments, institutions, and processes; and offers observations of the politics of developing further governance. The most important multilateral environmental agreement is the Convention on Biological Diversity. Governance of such conservationist synthetic biology is vital but gaps remain. The further development of governance is a political process, and conservationist synthetic biology has a political landscape that is atypical for emerging technologies.
ARRIGE 2020 Meeting | The promise of CRISPR and gene drive systems to end malaria in Africa
15145E. Gomez-Diaz, ARRIGE org, 2020-11-16 17:08:32.
Presentation by Elena Gómez Díaz (IPBLN-CSIC, Granada, Spain) at the ARRIGE 2020 meeting on "The promise of CRISPR and gene drive systems to end malaria in Africa". Discussion is included at the end of the Ruud de Maagd presentation.https://youtu.be/te3MJ8EZoes
Further guidance required for assessment of gene drive technology, says EFSA
15137Euractiv, The World News Monitor, 2020-11-16 16:25:26.
Existing guidelines are adequate for evaluating risks associated with gene-drive modified insects, but further guidance is needed for some areas, most notably for environmental risk assessments. The evaluation was requested to explore the issue ahead of the consideration of any possible applications of the technology and is also designed to support the EU in discussions on the biosafety of GMOs in international fora such as the United Nations. It found that while existing guidelines are sufficient for evaluating risks associated with technology, further guidance is needed for some areas, such as molecular characterisation, environmental risk assessment and post-market environmental monitoring.
Mutagenic chain reaction cannot be sufficiently controlled
15135Christoph Then, Testbiotech, 2020-11-16 16:21:27.
The European Food Safety Authority (EFSA) has published the results of its public consultation on the risks of so-called gene drive organisms. Testbiotech accuses the authority of disguising the real dimension of the risks. Gene drives are designed to spread artificial genetic constructs throughout populations of wild species much faster than would be expected naturally. Currently, gene drives are being developed with the aid of tools such as the CRISPR/Cas gene scissors. There are plans, e.g. to apply gene drives in insects (flies and mosquitoes) or rodents (rats or mice). The aim is to replace or eradicate natural populations. Once started the process cannot be controlled effectively or reliably. The damage to humans, the environment and nature could be severe.
Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives
15043E. Panel o. G. M. Organisms, H. Naegeli, J.-L. Bresson, T. Dalmay, I. C. Dewhurst, M. M. Epstein, P. Guerche, J. Hejatko, F. J. Moreno, E. Mullins, F. Nogué, N. Rostoks, J. J. Sánchez Serrano, G. Savoini, E. Veromann, F. Veronesi, M. B. Bonsall, J. Mumfor, EFSA Journal, 18:e06297. 2020-11-12 19:24:46.
As a proactive measure, the European Food Safety Authority (EFSA) has been requested by the European Commission to review whether its previously published guidelines for the risk assessment of genetically modified animals (EFSA, 2012 and 2013), including insects (GMIs), are adequate and sufficient for GDMIs, primarily disease vectors, agricultural pests and invasive species, for deliberate release into the environment. Under this mandate, EFSA was not requested to develop risk assessment guidelines for GDMIs. In this Scientific Opinion, the Panel on Genetically Modified Organisms (GMO) concludes that EFSA's guidelines are adequate, but insufficient for the molecular characterisation (MC), environmental risk assessment (ERA) and post-market environmental monitoring (PMEM) of GDMIs. While the MC,ERA and PMEM of GDMIs can build on the existing risk assessment framework for GMIs that do not contain engineered gene drives, there are specific areas where further guidance is needed for GDMIs.
Outcome of a public consultation on the draft adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives
15040European Food Safety Authority, Y. Devos, M. B. Bonsall, F. Nogué, K. Paraskevopoulos, E. A. Wimmer and L. G. Firbank, EFSA Supporting Publications, 17:1939E. 2020-11-12 19:10:10.
The European Food Safety Authority (EFSA) carried out an online public consultation to receive input from interested parties/persons on the draftscientific opinion on the adequacy and sufficiencyevaluation of existing guidelines for the molecular characterisation (MC), environmental risk assessment (ERA) and post-market environmental monitoring (PMEM) of genetically modified insects containing engineered gene drives. This draft scientific opinion was endorsed by the EFSA Panel on Genetically Modified Organisms (GMOs) for public consultation on 29 January 2020, and prepared by EFSA'sGene Drive expert Working Group and scientific officers. The public consultation was open from 17 February 2020 until 24 April 2020.
EFSA advises on risk assessment of engineered gene drives
15069EFSA, European Food and Safety Authority, 2020-11-12 18:15:34.
EFSA’s existing guidelines for the risk assessment of genetically modified animals are adequate for evaluating risks associated with gene drive modified insects. However, further guidance is needed for some areas, such as molecular characterisation, environmental risk assessment and post-market environmental monitoring, say EFSA’s experts on Genetically Modified Organisms.
Gene drives, species, and compassion for individuals in conservation biology
15072Y. Rohwer, Ethics, Policy and Environment, 2020-11-10 18:20:29.
In this paper I argue that these compassionate conservationists have a moral obligation to support the investigation and development of genetic modification technologies because of their potential to minimize suffering and eliminate killing in conservation. Furthermore, I will end the paper by suggesting that these genetic technologies can help avoid actions that could be damaging to one's moral character.
NIH NExTRAC (Novel and Exceptional Technology and Research Advisory Committee) | Workshop
15015NIH Office of Science Policy, National Institutes of Health (NIH), 2020-11-09 19:56:25.
NExTRAC provides advice to the Director of the National Institutes of Health (NIH) on matters related to the conduct and oversight of research involving emerging technologies in biomedical science. NExTRAC also makes recommendations on research involving the use of, and developments in, emerging biotechnologies and will address scientific, safety, ethical, and social issues associated with areas of emerging biotechnology research for which the NIH requests advice or guidance. One of the technologies this committee is considering is gene drive. The November 2020 meeting was a workshop: GENE DRIVES: BIOSAFETY GUIDANCE AND CONDITIONS FOR FIELD RELEASE RESEARCH
When Extinction is Warranted: Invasive Species, Suppression-Drives, and the Worst-Case Scenario
15050A. C. Thresher, Ethics, Policy and Environment, 2020-11-09 19:31:52.
The focus of this paper is on one such risk ? the danger of a suppression-drive escaping containment and wiping out the target species globally. Here, I argue that in most cases this risk is significant enough to warrant holding off on the technology. In some cases, however, we can bypass the precautionary principle by using a dominance approach that hinges on what I term the ?Worst-Case Clause?. This clause, in turn, provides us with a litmus test that can be fruitfully used to determine what species are viable targets for suppression-drives in the wild. Using this metric in concert with other considerations, I suggest that only three species are currently possible viable targets ? the European rabbit, ship rat, and Caribbean Tree Frog.
Brave New Planet: Reshaping Nature Through Gene Drives
15047E. Lander, Brave New Planet, 2020-11-09 19:26:24.
A new technology, called gene drives, has the power to spread any genetic instructions you wish across an entire animal or plant species in the wild. It might let us restore ecosystems ravaged by invasive species, or help species adapt to climate change. And, it might save millions of children from dying of malaria. But could altering nature in this way, and on this scale, have unintended consequences? And, when it comes reshaping ecosystems, who needs to say yes?
Gene drive blocks malaria transmission in mosquitoes
15035labonline, labonline, 2020-11-09 15:46:59.
Employing a strategy known as ‘population modification’, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California (UC) researchers have made a major advance in the use of genetic technologies to control the transmission of malaria parasites. Their work has been published in the journal Nature Communications.
The ethical way to alter organisms
15033K. Esvelt, Boston Globe, 2020-11-09 15:42:31.
As my colleagues and I first described in 2014, we can use CRISPR genome editing to duplicate the most powerful form of “gene drive,” a ubiquitous natural phenomenon that happens when a genetic change is inherited more frequently than usual. Encode the CRISPR machinery next to a useful edit we’ve made in the genome, and genome editing will reoccur in every generation, replacing the original with the edited version without limit. In principle, releasing such organisms would gradually alter entire wild populations and associated ecosystems.
Gene Drives: A Controversial Tool to Fight Malaria
15008H. Albert, LABIOTECH.eu, 2020-11-09 15:41:52.
The possibility of creating gene drives was introduced into the scientific community in 2003 by Austin Burt, a professor at Imperial College London. Burt was studying ‘selfish genes’ that can copy themselves into a specific target DNA sequence. He suggested that these genes, called homing endonucleases, could be used to make the majority of an organism’s offspring inherit a specific gene, instead of only half of it. This technology has a lot of potential. For example, it could be used to decimate populations of malaria-carrying mosquitoes by making the majority of their offspring male. However, there are concerns about the permanent nature of these genetic modifications and whether it could cause irreparable damage to the ecosystem it is used in.
Expert advises farmers to adopt gene drive-based pest control technology
15029S. Thompson, naija247news, 2020-11-09 15:36:25.
Dr Rose Gidado, County Coordinator, Open Forum on Agricultural Biotechnology(OFAB), has advised farmers to adopt the gene drive-based pest control technology. Gidado, also Deputy Director, National Biotechnology Development Agency (NABDA), said the adoption would significantly help to restore Nigeria’s food crop industry. According to her, Nigerian agricultural system is dominated by the application of synthetic pesticides which have resulted in environmental pollution. Gidado said that it had contributed greatly to climate change, with lethal consequences like increased pest attack, decreased crop yield and extreme heat stress in plants. The scientist said the application of gene drive in Nigeria’s agricultural system, would help greatly in the control of deadly insect pests which cause damages to crops and reduction in food production.
GeneConvene Global Collaborative | Research and Innovation for biodiversity: what role for gene drive research?
14968EP Intergroup CCBSD, European Bureau of Conservation and Development, 2020-11-06 19:06:04.
This webinar will provide an overview of how gene drive works and the problems it seeks to solve, introduce the most advanced research projects on gene drive in the sector of public health and conservation and present the work that international and European bodies such as WHO, IUCN and EFSA are carrying out on gene drive. It will also be an opportunity to address any questions participants may have with regards to gene drive and stimulate an open debate on the safe and responsible development of the research in this field.
Modeling CRISPR gene drives for suppression of invasive rodents
15003S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer, bioRxiv, 2020.11.05.369942. 2020-11-05 15:27:54.
Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit and allows for overlapping generations and a fluctuating population size. Our model includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters.
A gene-drive rescue system for the modification of malaria mosquito populations
14901A. Adolfi, Nature Research Bioengineering Community, 2020-11-03 18:48:29.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.
UC researchers pioneer more effective method of blocking malaria transmission in mosquitoes
14898UCI, UCI News, 2020-11-03 14:11:01.
University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to transmitting malaria parasites by increasing gene drive effectiveness in female mosquito progeny.The second-generation gene drive system described in this paper can be applied to any of the several thousand genes that are essential for insects to survive or reproduce,” said UC San Diego Distinguished Professor Ethan Bier, a co-author of the study and science director at the Tata Institute for Genetics and Society. “While it was developed in fruit flies, this system is readily transportable to a broad selection of insect species that serve as vectors for devastating disorders such as Chagas disease, sleeping disease, leishmaniasis and arboviral diseases.”
Is Gene Editing the Answer to Eradicating Malaria in Africa?
14885Staff, ASH Clinical News, 2020-11-01 16:00:02.
Researchers are looking at a new technique to eradicate malaria: Engineering mosquitoes with a “gene drive” – a gene that when inserted into mosquitoes (or other organisms) will be passed on to nearly 100% of the offspring in the next generation, rather than just half the offspring – that rapidly spreads a mutation that removes the insects’ ability to spread the malaria-causing parasite.
Gene Drives across engineered fitness valleys: Modeling a design to prevent drive spillover.
14880F. J. H. de Haas and S. Otto, bioRxiv, 2020.10.29.360404. 2020-10-29 15:44:22.
We model a proposed drive system that transitions in time from a low threshold drive system (homing-based gene drive) to a high threshold drive system (underdominance) using daisy chain technology. This combination leads to a spatially restricted drive strategy while maintaining an attainable release threshold.
Interview with Professor Austin Burt: Role of gene drive technology in the context of the EU’s Biodiversity Strategy 2030
14874S. Dunphy, European Scientist, 2020-10-28 14:10:38.
In view of these conditions, leading scientists are calling on EU institutions to continue to back research into gene drive as a potential tool to protect public health and deliver on Europe’s biodiversity goals. Experts believe gene drive technologies could be a vital and effective solution in developing countries and islands, as well as across Europe.
Inauguration and first meeting of WA-IVM Technical Working Groups
14872AUDA-NEPAD, AUDA-NEPAD News, 2020-10-27 19:37:33.
African Union Development Agency – NEPAD (AUDA-NEPAD) in collaboration with the West Africa Health Organization (WAHO), the Ministry of Health and the Ministry of Environment in Cote d’Ivoire, organized the inaugural meeting of WA-IVM Technical Working Groups (TWGs) from 24 – 26 April, 2019, in Abidjan, Cote d’Ivoire. Dr. ABLE, Inspector General of the Ministry of Health and Public Hygiene, representing the Minister, co-chaired the opening ceremony with Mr LAVRY, Technical Advisor of the Ministry of Environment and Sustainable Development.
Gene Drive: The What, How, Why, and Whether We Should
14865N. Pazhayam, The Pipettepen, 2020-10-26 19:12:07.
Under regular Mendelian inheritance, the probability of inheriting a particular allele from a heterozygous parent is 50% – this is because offspring can only inherit one or the other chromosome from each parent. However, gene drive is a technology that changes this probability and makes it much higher than 50%.
GeneConvene Global Collaborative Webinar Series | Engineered Gene Drives: Policy and Regulatory Considerations Webinar Series October-December 2020
14808Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2020-10-22 19:38:17.
In this series of webinars the regulatory and policy challenges of moving new innovative genetic biocontrol products such as gene drive technologies to the field will be featured. Each seminar is ~60 minutes in length followed by questions and answers.
WHO Refers to GM Mosquitoes as Beneficial Technology
14820ISAAA, Crop Biotech Update, 2020-10-21 17:27:43.
The World Health Organization (WHO) released its official statement to clarify its stance on the evaluation and use of genetically modified (GM) mosquitoes and its use to control vector-borne diseases (VBD). WHO says it supports the investigation of all potentially beneficial technologies, and these include GM mosquitoes.
Position of ARRIGE Scientific Committee on Gene Drive
14801ARRIGE Scientific Committee on Gene Drive, ARRIGE Newsletter, 2020-10-21 15:16:40.
We are facing a change of paradigm that must lead us to be responsible for altered inheritance and the hybridization between artefacts, considered as natural or artificial, at the very moment when this division itself is blurred by the engineering capacity to act on mutations, without knowing in advance the possibly adverse, short or long term, side effects, on the manipulated and other connected species.
Researchers help complete world first wasp genome project
14798Staff, The National Tribune, 2020-10-21 15:12:01.
In a world first, New Zealand researchers have sequenced the genome of three wasps, two of which are invasive wasps in New Zealand, paving the way for new methods of control for these significant pests.
Researchers complete world first wasp genome project
14796University of Otago, Phys Org, 2020-10-21 15:07:20.
In a world first, New Zealand researchers have sequenced the genome of three wasps, two of which are invasive wasps in New Zealand, paving the way for new methods of control for these significant pests.
Vector-Focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies
15960E. M. Rocha, R. D. Katak, J. C. de Oliveira, M. D. Araujo, B. C. Carlos, R. Galizi, F. Tripet, O. Marinotti and J. A. Souza, Tropical Medicine and Infectious Disease, 5. 2020-10-20 18:16:39.
Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put into research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the optimization of conventional and development of innovative vector-control tools.
Progress Toward Zygotic and Germline Gene Drives in Mice
14852C. Pfitzner, M. A. White, S. G. Piltz, M. Scherer, F. Adikusuma, J. N. Hughes and P. Q. Thomas, The CRISPR Journal, 3:388-397. 2020-10-20 17:17:24.
Here, we investigated the efficiency of CRISPR-Cas9-based gene drives in Mus musculus by constructing "split drive" systems where gRNA expression occurs on a separate chromosome to Cas9, which is under the control of either a zygotic (CAG) or germline (Vasa) promoter.
Fruit fly breakthrough puts killer mozzies on notice
14812V. Tressider, The Lighthouse, 2020-10-19 15:34:08.
A new designer fruit fly paves the way for scientists to replace disease-carrying mosquitoes with harmless, genetically modified versions, says Macquarie University researcher Dr Maciej Maselko.
WHO Releases a Position Statement on Genetically Modified Mosquitoes for the Control of Vector-Borne Diseases
14793E. R. Fletcher, Health Policy Watch, 2020-10-19 14:56:43.
WHO announced their support for the continued investigation into genetically modified mosquitoes as an alternative to existing interventions to reduce or prevent vector-borne diseases.
MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics
14733S. L. Wu, J. B. Bennett, H. M. Sanchez C, A. J. Dolgert, T. M. Leon and J. M. Marshall, bioRxiv, 2020.10.16.343376. 2020-10-17 15:42:27.
We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): an extension of and development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations.
Ethics and vector-borne diseases
14904Geneva: World Health Organization, WHO Guidance, 2020-10-14 18:57:10.
The guidance was developed by an international group of experts in vector control, infectious disease ethics, maternal and child health, ecology and climate change, research and vaccine development, and public health communication. It examines a broad range of ethical considerations related to VBD prevention and control, including the social and environmental determinants of health; vector control methods, including emerging technologies; screening, surveillance and research; vaccine campaigns; and mass drug administration.
Driven to Exterminate
14724Z. Moloo and J. Thomas, etc group, 2020-10-14 18:16:08.
Gates’s ‘let’s deploy it’ response may not seem out of character, but it was an unusually gung ho response given how risky the technology is widely acknowledged to be.
GeneConvene Global Collaborative Webinar Series | Gene Drive Policy and Regulatory Considerations 2020
14677Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2020-10-13 17:50:24.
This is series of webinars the regulatory and policy challenges of moving new innovative genetic biocontrol products such as gene drive technologies to the field will be featured.
ESA Position Statement on the Importance of Continued Innovation in Gene Drive Technology
14700Entomological Society of America, Annals of the Entomological Society of America, 2020-10-13 17:39:58.
The risks and benefits of GDTs should be considered with the risks and benefits of continuing current pest control interventions, which may be comparatively less effective or pose exposure risks to human health and the environment.
GeneConvene Global Collaborative Webinar Series | Gene Drive Policy and Regulatory Consideration
14670Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2020-10-13 17:34:35.
This is series of webinars the regulatory and policy challenges of moving new innovative genetic biocontrol products such as gene drive technologies to the field will be featured.
Evaluation of genetically modified mosquitoes for the control of vector-borne diseases
14661Global Malaria Programme, WHO - Position Statement, 2020-10-13 15:58:38.
In the spirit of fostering innovation, WHO takes the position that all potentially beneficial new technologies, including GMMs, should be investigated to determine whether they could be useful in the continued fight against diseases of public health concern. Such research should be conducted in steps and be supported by clear governance mechanisms to evaluate the health, environmental and ecological implications
GeneConvene Global Collaborative Webinar Series | Gene Drive Technical Webinars
14347David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2020-10-12 02:54:40.
A series of technical webinars on engineered gene drive technology research and development given by leading researchers in the field.
Engineering the Composition and Fate of Wild Populations with Gene Drive
14731B. A. Hay, G. Oberhofer and M. Guo, Annual Review of Entomology, 2020-10-09 15:37:03.
We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.
Towards rangatiratanga in pest management? Maori perspectives and frameworks on novel biotechnologies in conservation
14653S. Palmer, O. R. Mercier and A. King-Hunt, Pacific Conservation Biology, 11. 2020-10-09 13:58:04.
We gathered Maori perspectives on novel biotechnological controls for pest wasps through three distinct studies. Study participants included tertiary students, businesses, and spiritual or religiously affiliated groups. All participants drew from their identities as Maori people to help identify their position on these issues.
Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control
14647M. P. Su, M. Georgiades, J. Bagi, K. Kyrou, A. Crisanti and J. T. Albert, Parasites and Vectors, 13:507. 2020-10-07 13:33:23.
We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages.
Standardizing the definition of gene drive
319582020-10-01 13:25:21.
Gene Drives Could Kill Mosquitoes And Suppress Herpesvirus Infections
14588A. Berezow, American Council on Science and Health, 2020-09-30 20:03:47.
A team of researchers writing in the journal Nature Communications has shown that a gene drive can be used to suppress infection with cytomegalovirus, a type of herpesvirus.
Embracing Dynamic Models for Gene Drive Management
14596A. J. Golnar, E. Ruell, A. L. Lloyd and K. M. Pepin, Trends in Biotechnology, 2020-09-30 13:54:04.
We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology development and implementation.
Do Africans Want Genetically Modified Mosquitoes?
14591U. Effiong, The Pursuit, 2020-09-30 13:38:38.
The recent publication by fellow Nigerian scientists—Patricia Okorie and colleagues—originally drew my attention to the issue of GMMs.
Gene Drive: Modern Miracle or Environmental Disaster
14491K. Brooks, Journal of Law, Technology and Policy, 2020-09-25 19:57:31.
This Note will show how gene drive technology fits imperfectly into the old regulatory framework through case studies. The Analysis will also describe how the different regulatory agencies handle similar gene drive-like organisms inconsistently, and the inherent danger of this approach considering upcoming developments in the field.
Resistance to natural and synthetic gene drive systems
14468T. A. R. Price, N. Windbichler, R. L. Unckless, A. Sutter, J.-N. Runge, P. A. Ross, A. Pomiankowski, N. L. Nuckolls, C. Montchamp-Moreau, N. Mideo, O. Y. Martin, A. Manser, M. Legros, A. M. Larracuente, L. Holman, J. Godwin, N. Gemmell, C. Courret, A. Buc, Journal of Evolutionary Biology, 2020-09-24 17:20:31.
This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in genera
Gene Drive Control Worry Eased by Genetic Neutralizing Elements
14452Staff, Genetic Engineering and Biotechnology News, 2020-09-21 17:17:09.
Bier and his colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild, offering two new solutions based on elements developed in the common fruit fly. T
Global citizen deliberation on genome editing
14607J. S. Dryzek, D. Nicol, S. Niemeyer, S. Pemberton, N. Curato, A. Bächtiger, P. Batterham, B. Bedsted, S. Burall, M. Burgess, G. Burgio, Y. Castelfranchi, H. Chneiweiss, G. Church, M. Crossley, J. de Vries, M. Farooque, M. Hammond, B. He, R. Mendonça, J., Science, 369:1435. 2020-09-18 18:32:40.
Here we show how, as the global governance vacuum is filled, deliberation by a global citizens' assembly should play a role, for legitimate and effective governance.
Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives
14444X.-R. S. Xu, E. A. Bulger, V. M. Gantz, C. Klanseck, S. R. Heimler, A. Auradkar, J. B. Bennett, L. A. Miller, S. Leahy, S. S. Juste, A. Buchman, O. S. Akbari, J. M. Marshall and E. Bier, Molecular Cell, 2020-09-18 11:30:45.
Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs).
Biologists create new genetic systems to neutralize gene drives
14442University of California San Diego, ScienceDaily, 2020-09-18 11:24:50.
Now, scientists at the University of California San Diego and their colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild.
Risks of releasing gene drives mosquitoes – a possible future scenario
15143Testbiotech, 2020-09-17 17:01:45.
Genetically engineering the genome of an organism with gene drive means that it will be replicated in every following generation. This allows the altered gene to spread rapidly throughout natural populations, which may be decimated or even eradicated. The video contains both factual and fictional content (the latter marked as „possible future scenario“). The fictional content shows the possible future consequences of using gene drive technology - and is intended to stimulate broad public debate. Civil society needs to engage intensively with issues around new developments in the field of biotechnology and genetic engineering.
A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population
14387J. Champer, E. Yang, E. Lee, J. Liu, A. G. Clark and P. W. Messer, Proceedings of the National Academy of Sciences, 202004373. 2020-09-14 15:23:07.
Here, we present a CRISPR homing drive that was able to successfully spread to all individuals in a laboratory cage study in Drosophila melanogaster without any apparent evolution of resistance.
Why the UK could end up deploying risky gene drives while ignoring natural biological control
14385J. Mathews, GM Watch, 2020-09-14 15:10:57.
First they cloned Dolly the sheep. Now they’re targeting grey squirrels
The Evolving Arsenal Against Mosquito-Born Diseases
14369J. Smith, Labiotech.eu, 2020-09-10 16:01:02.
As the global climate continues to warm, disease-spreading mosquitoes such as Aedes aegypti are expected to establish themselves in the US and Europe.
Teach Me in 10 – Gene Drive Research with Dr. Jennifer Baltzegar
14362J. Baltzegar, Technology Networks, 2020-09-10 15:44:16.
Dr Baltzegar teaches us about how the maturation of genetic engineering approaches has advanced gene drives, the two different strategies for gene drives and some of the key questions surrounding the application of gene drives in society.
Underlying beliefs linked to public opinion about gene drive and pest-specific toxin for pest control
14331E. A. MacDonald, E. Edwards, J. Balanovic and F. Medvecky, Wildlife Research, 2020-09-08 18:03:31.
Public engagement that acknowledges and responds to these underlying beliefs, rather than a traditional campaign based on biodiversity and environmental gains, may be more effective at creating a constructive dialogue about if and how these tools should be used, and to avoid replicating the polarised debate about 1080.
Engineering speciation events in insects may be used to control harmful pests
14328University of Minnesota, Phys Org, 2020-09-08 17:55:45.
A team of scientists led by Mike Smanski, Ph.D., in the College of Biological Sciences (CBS) has generated speciation events in fruit flies so that engineered strains can reproduce normally with each other, but mating with unmodified flies results in non-viable offspring.
Prospects and Pitfalls: Next-Generation Tools to Control Mosquito-Transmitted Disease
14366E. P. Caragata, S. Dong, Y. Dong, M. L. Simões, C. V. Tikhe and G. Dimopoulos, Annual Review of Microbiology, 74:455-475. 2020-09-08 15:57:19.
A diverse array of next-generation tools has been designed to eliminate mosquito populations or to replace them with mosquitoes that are less capable of transmitting key pathogens.
Generating single-sex litters: development of CRISPR-Cas9 genetic tools to produce all-male offspring
14343C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, O. A. Ojarikre, P. J. Ellis and J. M. A. Turner, bioRxiv, 2020.09.07.285536. 2020-09-07 18:52:30.
Using the mouse as a model, we developed a synthetic, two-part bicomponent strategy for generating all-male litters.
Suppressing evolution in genetically engineered systems through repeated supplementation
15188N. C. Layman, B. M. Tuschhoff, A. J. Basinski, C. H. Remien, J. J. Bull and S. L. Nuismer, Evolutionary Applications, 12. 2020-09-05 15:21:40.
Genetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms. One potential method to limit unwanted evolution is by taking advantage of the ability of gene flow to counter local adaption, a process of supplementation. Here, we investigate the feasibility of supplementation as a mechanism to offset the evolutionary degradation of a transgene in three model systems: a bioreactor, a gene drive, and a transmissible vaccine.
Scientists Evaluate Environmental Impacts of Gene Drive Organisms
14334Staff, American Laboratory, 2020-09-04 18:06:56.
Researcher Marion Dolezel, from the Environment Agency Austria, and a team of international scientists published in the open-access journal BioRisk, discuss the potential risks and impacts on the environment.
Inherently confinable split-drive systems in Drosophila
14294G. Terradas, A. B. Buchman, J. B. Bennett, I. Shriner, J. M. Marshall, O. S. Akbari and E. Bier, bioRxiv, 2020.09.03.282079. 2020-09-03 14:16:46.
Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that were inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). I
Do Africans need genetically modified mosquitoes?
14261genetically modified, mosquito, oxitec, autocidal, SIT, perspective, malaria, gene drive synthetic, engagement,, Mail and Guardian, 2020-09-01 14:32:06.
The following is an updated version of an article I wrote for the University of Michigan Risk Science Centre a while ago:
Governing New Biotechnologies for Biodiversity Conservation: Gene Drives, International Law, and Emerging Politics
14258J. L. Reynolds, Global Environmental Politics, 20:28-48. 2020-08-31 14:28:38.
This article describes and analyzes the international law and politics of gene drives’ research, development, and possible use, with an emphasis on their potential biodiversity applications.
Non-GMO approach reduces cases of mosquito-borne dengue by 77%
14239GM Watch, GM Watch, 2020-08-31 13:55:39.
A randomized field trial found that mosquitoes infected with a natural bacterium called Wolbachia reduced cases of dengue by an "extraordinary" 77%.
Bacteria-Laced Mosquitoes Limit Spread of Dengue
14244A. Heidt, The Scientist, 2020-08-29 14:05:32.
Researchers have infected Aedes aegypti mosquitoes—the species responsible for passing on many diseases—with bacteria called Wolbachia with the intent of reducing the insects’ ability to pass on dengue to people.
Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex
15277S. Dhole, A. L. Lloyd and F. Gould, Annual Review of Ecology, Evolution, and Systematics, 51:505-531. 2020-08-28 21:09:09.
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theoretical possibility, gene drive spread in natural populations is more complex and merits a more realistic assessment. The fate of any gene drive released in a population would be inextricably linked to the population’s ecology. Given the uncertainty often involved in ecological assessment of natural populations, understanding the sensitivity of gene drive spread to important ecological factors is critical. Here we review how different forms of density dependence, spatial heterogeneity, and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.
Chromosome drives via CRISPR-Cas9 in yeast
15025H. Xu, M. Han, S. Zhou, B.-Z. Li, Y. Wu and Y.-J. Yuan, Nature Communications, 11:4344. 2020-08-28 15:22:50.
Our results show that the entire Saccharomyces cerevisiae chromosome can be eliminated efficiently through only one double-strand break around the centromere via CRISPR-Cas9. As a proof-of-concept experiment of this CRISPR-Cas9 chromosome drive system, the synthetic yeast chromosome X is completely eliminated, and the counterpart wild-type chromosome X harboring a green fluorescent protein gene or the components of a synthetic violacein pathway are duplicated by sexual reproduction. We also demonstrate the use of chromosome drive to preferentially transmit complex genetic traits in yeast.
Scientists infect mosquitoes with bacteria to stop the transmission of dengue fever in Indonesia, dropping infection rates by 77 percent
14250D. Avery, Daily Mail, 2020-08-28 14:15:52.
The team found that dengue infections were 77 percent lower in treated neighborhoods, compared to areas not exposed to the infected insects.
Evading evolution of resistance to gene drives
14174R. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020-08-27 14:29:17.
Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially.
Novel combination of CRISPR-based gene drives eliminates resistance and localises spread
14172N. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc, bioRxiv, 2020-08-27 14:22:46.
We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses.
The mosquito strategy that could eliminate dengue
14170E. Callaway, Nature, 2020-08-27 14:19:52.
The study, conducted in an Indonesia city, showed that releasing mosquitoes modified to carry a bacterium called Wolbachia, which stops the insects from transmitting some viruses, led to a steep drop in cases of dengue fever.
Researchers Find New Approach To Control Dengue, Zika By Genetically Modifying Mosquitoes
14247N. Sharma, R. Republicworld.com, 2020-08-27 14:11:56.
A new study carried out in Indonesia has shown that dengue infection rates decreased in regions where the genetically modified mosquitoes were introduced.
Australian research takes aim at dengue, another killer virus
14226E. Connors, Finanacial Review, 2020-08-26 20:22:39.
Australian researchers have teamed up with Indonesian philanthropists to strike a blow against dengue fever, the deadly disease that was a growing scourge in south-east Asia and South America long before COVID-19.
Australian scientists slash dengue fever in Indonesia by infecting mosquitoes with bacteria
14224A. Barker, ABC News, 2020-08-26 20:17:56.
Australian scientists may have found the secret to eradicating dengue fever, with a lengthy trial in Indonesia drastically reducing the incidence of the mosquito-borne virus.
Anthony James / Mosquito Modification
14229Big Picture Science, SETI Institute, 2020-08-24 20:26:09.
Anthony James, vector biologist at the University of California, Irvine, describeshow we might genetically modify mosquitoes to make them unable to pass malaria on to humans.
Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae
14015R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James, Proceedings of the National Academy of Sciences, 202010214. 2020-08-24 12:38:12.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.
A home and rescue gene drive forces its inheritance stably persisting in populations
14006N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. Akbari, bioRxiv, 2020.08.21.261610. 2020-08-23 17:46:58.
We demonstrate that HomeR can achieve nearly ~100% transmission enabling it to persist at genotypic fixation in several multi-generational population cage experiments, underscoring its long term stability.
Viewpoint: Is there a scientific basis to ban gene drive technology that can rid us of virus-carrying rodents and mosquitoes?
13845K. Vavitas, Genetic Literacy Project, 2020-08-18 13:51:23.
Gene drives may be invaluable tools to control the spread of parasites, invasive species, and disease carriers. But the technology has faced strong opposition from activist groups and some mainstream scientists based on environmental and food safety. Are these concerns valid?
Researchers’ Plan To Release Genetically Engineered American Chestnut Trees in Forests Will Set Dangerous Precedents If Approved
13890Global Justice Ecology Project, Common Dreams, 2020-08-18 13:20:50.
Researchers are working with the United States Department of Agriculture (USDA) to finalize a petition requesting the unprecedented approval of a genetically engineered (GE or genetically modified) tree designed to be planted in our forests and spread freely in the wild. Once the internal petition process is complete, the USDA will release it for public comment. This is expected to occur at any time.
Towards Responsive Eco-technology: The Development of a Male Sex-biased Mouse
24607W. Kamau, Massachusetts Institute of Technology, 2020-08-16 08:55:45.
CRISPR-Cas systems have catalyzed the emergence of several synthetic population management strategies, like gene drives, for controlling pests and disease vectors. As these technologies garner greater visibility in both general and regulatory audiences, questions have arisen about the invasiveness of drive strategies and have underscored a need for community guidance in designing population management technologies. In heterogametic species, an engineered male-determining chromosome can serve as a method for providing robust and localized population suppression without the need for a gene drive. In mice, X-chromosome inactivation is mediated by X-inactive specific transcript (Xist) long non-coding RNA. I propose to encode a system on the Y chromosome to knock out a necessary region for proper X-inactivation in females. Loss of Xist gene function has no known effects in males or females with a dysfunctional maternal copy, however, females who inherit a dysfunctional paternal copy die at embryonic day 8.5. Thus, this results in a male sex-biased mouse. To create a daughterless mouse, my proof-of-principle design will include a constitutively expressed Cas protein with at minimum a two-guide array. Additionally, I will draw on the ecological species concept found in some cultures, like the M¯aori of New Zealand, to create an alternate eco-cisgenic version using cisgenic murine elements and a CRISPR system found in a commensal species of bacteria. Creating a cisgenic non-driving mammalian model of a genetic population suppression system would be a first-of-its-kind example to show how biological engineering design decisions can be congruent with culturally specific notions of ecology.
Bednets or Biotechnology: To Rescue Current Persons or Research for the Future?
14236D. E. Callies, Fudan Journal of the Humanities and Social Sciences, 14. 2020-08-13 13:44:08.
After an exploration of the duty to rescue and cost-effectiveness analysis, I suggest we look towards the literature on intergenerational justice for a justifiable answer to the question of how we ought to allocate our malaria resources.
Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility
13724A. R. North, A. Burt and H. C. J. Godfray, BMC Biology, 18:98. 2020-08-11 12:23:41.
Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. Here, we use simulation modelling to understand the factors affecting the spread of this type of gene drive over a one million-square kilometre area of West Africa containing substantial environmental and social heterogeneity.
Incorporating Characteristics of Gene Drive Engineered Ae. aegypti as Methods to Reduce Dengue and Zika Virus into the Bayesian Network – Relative Risk Model, Using Ponce, Puerto Rico as a Case Study
16097S. R. Eikenbary, WWU Graduate School Collection, 2020-08-10 19:24:02.
The Bayesian network relative risk model can perform the risk assessment of gene drive engineered Ae. aegypti for vector control and as part of an adaptive management strategy to reduce dengue and Zika transmission. This study illustrates how the BN-RRM can integrate gene drive related information within a risk assessment framework suitable for adaptive management of these novel stressors.
Engineered Reproductively Isolated Species Drive Reversible Population Replacement
13837A. Buchman, I. Shriner, T. Yang, J. Liu, I. Antoshechkin, J. M. Marshall, M. W. Perry and O. S. Akbari, bioRxiv, 2020.08.09.242982. 2020-08-10 15:42:26.
Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. We engineer multiple reproductively isolated SPECIES and demonstrate their threshold-dependent gene drive capabilities in D. melanogaster.
CRISPR gene drives could eliminate many vector-driven pests and diseases, but challenges remain
13631J. Champer, Genetic Literacy Project, 2020-08-06 14:11:01.
A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance.
Maintenance management and eradication of established aquatic invaders
13936D. Simberloff, Hydrobiologia, 22. 2020-08-06 13:34:15.
The rapid development of technologies based on genetics has engendered excitement about possibly eradicating or controlling terrestrial invaders, and such technologies may also prove useful for certain aquatic invaders. Methods of particular interest, alone or in various combinations, are gene-silencing, RNA-guided gene drives, and the use of transgenes.
Global Governing Bodies: A Pathway for Gene Drive Governance for Vector Mosquito Control
13605A. Kelsey, D. Stillinger, T. B. Pham, J. Murphy, S. Firth and R. Carballar-Lejarazú, American Journal of Tropical Medicine and Hygiene, 2020-08-05 12:34:11.
We examined the current institutions and governing bodies among various continents that could have an impact on gene drive governance or the potential to adapt to its future use. Possible governance strategies also are proposed that seek to bridge gaps and promote an ethically sound policy framework. Ideally, governance strategies should be developed before or at the same pace as gene drive research to anticipate field releases and maximize their impact as a public health tool.
Genomic analyses of a livestock pest, the New World screwworm, find potential targets for genetic control programs
13618M. J. Scott, J. B. Benoit, R. J. Davis, S. T. Bailey, V. Varga, E. O. Martinson, P. V. Hickner, Z. Syed, G. A. Cardoso, T. T. Torres, M. T. Weirauch, E. H. Scholl, A. M. Phillippy, A. Sagel, M. Vasquez, G. Quintero and S. R. Skoda, Nature Communications, 3:424. 2020-08-04 12:56:38.
We identify and analyze the expression of genes that are likely important for host-seeking behavior (chemosensory), development of larvae in open wounds in warm-blooded animals (heat shock protein, immune response) and for building transgenic strains for genetic control programs including gene drive (sex determination, germline). This study will underpin future experiments aimed at understanding the parasitic lifestyle of the screwworm fly and greatly facilitate future development of strains for efficient systems for genetic control of screwworm.
Fighting malaria with genetically modified mosquitoes
13609E. Nakkazi, BMJ, 370:m2172. 2020-08-04 12:53:14.
Could a bold project to genetically engineer mosquitoes curb the scourge of malaria in Africa? Finding out will require careful science—and public acceptance, writes Esther Nakkazi
Exploring gene drive’s role in fight against malaria
13536J. Conrow, Genetic Literacy Project, 2020-08-02 17:02:28.
J. Conrow (2020) Genetic Literacy Project. An international initiative has formed to ensure that gene drive technology gets a chance to prove its mettle in the quest to control malaria.
Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi
13593A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James, bioRxiv, 2020.08.02.233056. 2020-08-02 12:59:26.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion.
Biotechnologies in pest wasp control: taking the sting out of pest management for Māori businesses?
14710S. Palmer and O. R. Mercier, New Genetics and Society, 2020-07-31 19:13:18.
A Maori-centered mixed-method study gauged the perceptions of eight Maori businesses about the potential use of five specific new biotechnological controls in pest management.
Meet Cosmo, the gene-edited Crispr calf
13590S. D. McClain, Capital Press, 2020-07-31 12:56:28.
Cosmo was the grand finale of a series of experiments to create a line of genome-edited cattle tailored for the beef industry. He was designed to produce 75% male offspring.
Chemical controllable gene drive in Drosophila
13773D. Chae, J. Lee, N. Lee, K. Park, S. J. Moon and H. H. Kim, ACS Synthetic Biology, in press. 2020-07-30 12:48:10.
Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted in 7-12% removal of gene drive elements at each generation, leading to a significant reduction in gene drive-fly propagation.
Nix alone is sufficient to convert female Aedes aegypti into fertile males and myo-sex is needed for male flight
13780A. Aryan, M. A. E. Anderson, J. K. Biedler, Y. M. Qi, J. M. Overcash, A. N. Naumenko, M. V. Sharakhova, C. H. Mao, Z. N. Adelman and Z. J. Tu, Proceedings of the National Academy of Sciences of the United States of America, 117:17702-17709. 2020-07-28 13:17:04.
Here, we report the generation of multiple transgenic lines that express Nix under the control of its own promoter. Genetic and molecular analyses of these lines provided insights unattainable from previous transient experiments. We show that the Nix transgene alone, in the absence of the M-locus, was sufficient to convert females into males with all male-specific sexually dimorphic features and male-like gene expression.
Après les OGM, la nouvelle technique du forçage génétique inquiète écologistes et scientifiques
13595H. Leussier, Reporterre, 2020-07-28 13:04:33.
Les organismes issus du forçage génétique peuvent transmettre, sans autre intervention humaine, des gènes modifiés à tous leurs descendants. Cette technique permettrait d’éradiquer des espèces nuisibles, comme certains moustiques vecteurs de la malaria. Mais des associations, des scientifiques et des responsables politiques, inquiets de potentiels effets dévastateurs, réclament un moratoire international.
The potential for a CRISPR gene drive to eradicate or suppress globally invasive social wasps
13486P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean, Scientific Reports, 10:12398. 2020-07-24 17:41:41.
P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean (2020). Scientific Reports. doi: 10.1038/s41598-020-69259-6 Gene drives have potential for widespread and cost-efficient pest control, but are highly controversial. We examined a potential gene drive targeting spermatogenesis to control the invasive common wasp (Vespula vulgaris) in New Zealand.
A Crispr calf is born. It’s definitely a boy
13454M. Molteni, WIRED, 2020-07-24 16:25:14.
M. Molteni (2020). Wired. UC Davis scientists spent years editing a sex-determining gene into bovine embryos. In April, Cosmo arrived—and his DNA reveals how far the field has to go. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Scientists use CRISPR technology to insert sex-determining gene
13452A. Quinton, Phys Org, 2020-07-23 16:21:10.
A. Quinton (2020). Phys Org. Scientists at the University of California, Davis, have successfully produced a bull calf, named Cosmo, who was genome-edited as an embryo so that he'll produce more male offspring. The research was presented in a poster on July 23 at the American Society of Animal Science meeting. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Lettre ouverte a Monsieur le Premier Ministre demandant l’interdiction de la production, de l’utilisation et de la dissémination de tout OGM issu du forçage génétique
13447A. Bossu, N. Laarman, D. Houdebine, H. Le Meur, F. Jacquemart and F. Warlop, Open Letter, 2020-07-22 15:04:01.
A. Bossu, N. Laarman, D. Houdebine, H. Le Meur, F. Jacquemart and F. Warlop (2020). Open Letter. An open letter from French civil society organizations urging the French Parliament to support a resolution at the upcoming Convention on Biodiversity that would call for a moratorium on the release of organisms containing engineered gene drive technologies.
Providing a policy framework for responsible gene drive research: an analysis of the existing governance landscape and priority areas for further research
13231D. Thizy, I. Coche and J. de Vries, Wellcome Open Research, 2020-07-20 12:19:36.
D. Thizy, I. Coche and J. de Vries (2020). Wellcome Open Research. doi: 10.12688/wellcomeopenres.16023.1 In this manuscript, we review the existing regulatory landscape around gene drive research and map areas of convergence and divergence, as well as gaps in relation to guidelines for community engagement in gene drive research.
How do you make a gene drive mosquito?
13053GeneConvene Virtual Institute, GeneConvene Global Collaborative, 2020-07-17 14:10:32.
This short video explains and illustrates how transgenic mosquitoes are made in the laboratory. While mosquitoes are the focus of the video, the process shown is used to create transgenic insects of almost any species.
An argument for gene drive technology to genetically control populations of insects like mosquitoes and locusts
13196I. Ronai and B. Lovett, The Conversation, 2020-07-14 18:15:19.
The fate of society rests in part on how humans navigate their complicated relationship with insects – trying to save “good” insects and control “bad” ones. Some insects, like mosquitoes, bite people and make them sick – remember Zika? Now the U.S. mosquito season is already in full swing, with over 10 cases of Dengue fever reported in the Florida Keys this year. Some insects, like bees, are pollinators that help produce our food. Others, like locusts, currently threaten crops in East Africa and Asia, preferring to eat our food instead. Insects have proven themselves extremely capable at evolving strategies to get around control methods, such as chemical insecticides and habitat modification, and current pest control technologies are simply not keeping up.
Researchers convert female mosquitoes to nonbiting males with implications for mosquito control
13194Virginia Tech, ScienceDaily, 2020-07-14 18:12:22.
Researchers convert female mosquitoes to nonbiting males with implications for mosquito control Virginia Tech researchers have proven that a single gene can convert female Aedes aegypti mosquitoes into fertile male mosquitoes and identified a gene needed for male mosquito flight
Genome Editing in Food and Farming: Risks and unexpected consequences
13186J. Cotter and D. Perls, Canadian Biotechnology Action Network, 2020-07-14 17:53:41.
J. Cotter and D. Perls (2020). Canadian Biotechnology Action Network. In this report, we provide an overview of genome editing techniques being explored in agriculture, and the range of potential unexpected effects that can arise from them. The report draws on recent scientific publications, in a rapidly evolving field of research including gene drive and genetic biocontrol.
Socrates Untenured: Ethics, Experts, and the Public in the Synthetic Age
13182C. Preston, ISSUES in Science and Technology, 2020-07-14 17:44:20.
C. Preston (2020). Three tools have transformed biotechnology over the past decade and a half. Gene reading has made it possible to quickly sequence the genome of any living creature. Gene synthesis has made it possible to construct DNA sequences in the lab from constituent chemicals. Gene editing has made it possible to place those sections into an existing DNA sequence at any point a technician chooses.
CSOs raise alarm over genetically-engineered mosquitoes in Nigeria
13179A. Oboh, Vanguard, 2020-07-11 17:41:57.
No fewer than 75 civil society organisations, CSOs, across the world have raised the alarm over moves to release genetically-modified mosquitoes in Nigeria, noting that the country was about to be used as a guinea pig for the project, which will endanger humans, biodiversity and to ecosystem balance. The CSOs noted that the shortcoming of transgenic mosquitoes was evident from the experiments done in Brazil and in Burkina Faso.
Three innovative technologies stopping malaria
13168B. Muni, The Borgen Project, 2020-07-09 14:47:45.
Malaria has plummeted by 40% fifteen years after 2000. A report that NCBI published attributed this to mosquito preventative measures like bed netting and insecticides. These interventions and practices, like wearing light color clothing, help at-risk populations fight malaria. However, mosquitos are learning to fight back. Resistance to insecticides is evolving in mosquitos and malaria continues to afflict millions. In 2018, there were still 228 million cases of malaria and 405,000 deaths. Over 90% of these cases and deaths occurred in Sub-Saharan Africa, but there are many interventions that have the potential to stop malaria. Here are three innovative technologies stopping malaria.
2-Locus Cleave and Rescue; selfish elements harness a recombination rate-dependent generational clock for self limiting gene drive
13150G. Oberhofer, T. Ivy and B. A. Hay, bioRxiv, 2020-07-09 14:03:42.
Self-limiting gene drive allows control over the spread and fate of linked traits. Cleave and Rescue (ClvR) elements create self-sustaining drive and comprise a DNA sequence-modifying enzyme (Cas9-gRNAs, Cleaver) that disrupts an essential gene, and a tightly linked, uncleavable version of the essential gene (Rescue). ClvR spreads by creating conditions in which those without it die because they lack essential gene function. We show that when ClvR is implemented in a 2-locus format, with key elements – Rescue (and Cargo), and Cas9 and/or gRNAs – located at different genomic positions, spread of the Rescue is self-limiting. Drive strength and duration are determined by a recombination rate-dependent generational clock, providing an important point of control for different ecological and regulatory contexts. We implement 2-locus ClvR in Drosophila. Rescue spreads to high frequency in a Cas9-dependent manner, while the frequency of Cas9 decreases, demonstrating transient drive and loss of future drive potential.
Groups warn against release of genetically-engineered mosquitoes in Nigeria
13172C. Onyesi, Daily Post, 2020-07-07 14:52:15.
C. Onyesi (2020). Daily Post. Over 75 Civil Society Organizations from Nigeria, Africa and the world have condemned moves to open the way for the release of genetically modified mosquitoes in Nigeria.
Malaria: Over 75 CSOs raise alarm over plans to release nautically engineered mosquitoes
13174News Agency of Nigeria, WorldStage, 2020-07-06 14:56:01.
Mre than 75 Environmental Civil Society Organisations from Nigeria, Africa and other countries have condemned moves to open way for release of genetically modified mosquitoes to control malaria infection. The News Agency of Nigeria (NAN), reports that at a virtual meeting of the West African Integrated Vector Management Programme, on June 6, Mr Rufus Ebegba, Vice Chairman of the Programme said: “There is the need to accelerate the development of regulatory pathways for genetically based vector control methods such as transgenic mosquitoes.”
NGOs call for moratorium on controversial ‘gene drive organisms’
13170N. Foote, EURACTIV, 2020-07-03 14:50:12.
https://borgenproject.org/3-innovative-technologies-stopping-malaria/
Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives
12711V. López Del Amo, B. S. Leger, K. J. Cox, S. Gill, A. L. Bishop, G. D. Scanlon, J. A. Walker, V. M. Gantz and A. Choudhary, Cell Reports, 31:107841. 2020-06-30 20:53:02.
Summary Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of 50% dictated by Mendel’s law of gene segregation, making them a promising tool for population engineering. However, current technologies lack control over their propagation capacity, and there are important concerns about potential unchecked spreading. Here, we describe a gene-drive system in Drosophila that generates an analog inheritance output that can be tightly and conditionally controlled to between 50% and 100%. This technology uses a modified SpCas9 that responds to a synthetic, orally available small molecule, fine-tuning the inheritance probability. This system opens a new avenue to feasibility studies for spatial and temporal control of gene drives using small molecules.
Nigerian government restates commitment to safety in applying modern biotechnology
13164Agencies, today ng, 2020-06-30 14:41:51.
The National Biosafety Management Agency (NBMA) has reiterated its commitment to ensure the safety of the public while applying modern biotechnology to boost food security and economic development of citizens. Dr Rufus Ebegba, Director-General, NBMA, gave the assurance at a meeting to review the National Guidelines of the Regulation of Gene Editing, on Tuesday in Abuja. Ebegba said the NBMA was amended in 2019, to include the application of gene drive, gene editing and synthetic biology and biosecurity which says: ”No person, institution or body shall carry out gene drive, gene editing and synthetic biology except with the approval of the agency,”.
Please support a global moratorium on the environmental release of gene drive organisms
13160J. Riss, J. Munic and B. Harlin, Open Letter, 2020-06-30 14:34:22.
J. Riss, J. Munic and B. Harlin (2020). Open Letter. We, the undersigned civil society organizations, write to you to request that the EU Commission fully supports the EU Parliament's call for a global moratorium on the release of Gene Drive Organisms (GDOs). This is in view of the EU preparation for the upcoming Conference of the Parties (COP15) to the Convention on Biological Diversity (CBD) and the Cartagena Protocol on Biosafety (COP-MOP10).
Soon we’ll be able to engineer the wild, can the policies keep up with the science?
13158M. Montague and A. Kobokovich, The Hill, 2020-06-29 14:32:02.
Humans have been able to genetically alter the world around them for thousands of years. With the domestication of dogs at least 14,000 years ago, genetically modified organisms (GMOs) have been a constant feature of human society; only recently have we gained the ability to perform these modifications at the molecular level. Even more recently, gene drive technology has fundamentally added the ability of humans to modify wild organisms, not only domesticated organisms. With the ability to make rapid, permanent changes to wild species on the near horizon, we must act now to implement policies that will carefully regulate their use while allowing for vital scientific research to continue.
Role of gene drives in malaria elimination strategy: modeling impact and cost-effectiveness in the Democratic Republic of the Congo
12729N. Metchanun, C. Borgemeister, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, medRxiv, 2020-06-29 13:15:39.
The tremendous burden of malaria has led to renewed efforts on malaria elimination and the development of novel tools for application where existing tools fall short. Gene drive mosquitoes, where transgenes and their associated phenotypes are efficiently propagated to future generations, are under development to suppress vector populations or render vectors incapable of malaria transmission. However, the role of gene drives in an integrated elimination strategy is underexplored. Using a spatially explicit agent-based model of malaria transmission in the Democratic Republic of the Congo, we describe the impact of integrating a population suppression driving-Y gene drive into malaria elimination strategies. We find that as long as the driving-Y construct is extremely effective, releases of gene drive mosquitoes can eliminate malaria, and we identify a cost ceiling for gene drive to be cost-effective relative to existing tools. Vector control via gene drive is worth considering as a supplemental intervention when the construct parameters and costs are suitable.
Translating gene drive science to promote linguistic diversity in community and stakeholder engagement
12560C. Cheung, S. Gamez, R. Carballar-Lejarazú, V. Ferman, V. N. Vásquez, G. Terradas, J. Ishikawa, C. E. Schairer, E. Bier, J. M. Marshall, A. A. James, O. S. Akbari and C. S. Bloss, Global Public Health, 2020-06-26 18:55:10.
Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking publics should have equal access to such information, which is especially critical when the technology in question may impact whole communities. We convened an interdisciplinary workgroup to translate previously developed narrated slideshows on gene drive mosquitoes from English into Spanish, reviewing each iteration for scientific accuracy and accessibility to laypeople. Using the finalised stimuli, we conducted five online, chat-based focus groups with Spanish-speaking adults from California. Overall, participants expressed interest in the topic and were able to summarise the information presented in their own words. Importantly, participants asked for clarification and expressed scepticism about the information presented, indicating critical engagement with the material. Through collaboration with Spanish-speaking scientists engaged in the development of GE methods of vector control, we translated highly technical scientific information into Spanish that successfully engaged Spanish-speaking participants in conversations about this topic. In this manuscript, we document the feasibility of consulting Spanish-speaking publics about a complex emerging technology by drawing on the linguistic diversity of the scientific teams developing the technology.
Development of zygotic and germline gene drives in mice
12531C. Pfitzner, J. N. Hughes, M. A. White, M. Scherer, S. G. Piltz and P. Q. Thomas, bioRxiv, 2020-06-21 15:15:40.
Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing "split drive" systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters.
Research team genetically modifies mosquito; now completing construction of full gene drive system
12688University of Hawaii, UH Hilo News, 2020-06-18 20:23:40.
A research group at the University of Hawai‘i at Hilo is currently completing construction of the full gene drive system of the Hawai‘i-sourced southern house mosquito (Culex quinquefasciatus), and plan to use CRISPR technology to insert it alongside an eye-color phenotype marker. CRISPR allows researchers to easily alter DNA sequences and modify gene function.
Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes
13607P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller, Journal of Applied Ecology, 11. 2020-06-18 12:44:16.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this transgene in large cages using a joint experimental modelling approach. We performed a 4-month experiment in large, indoor cages to study the population genetics of the transgene.
ENSSER | Gene Drive Webinar Series
12568European Network of Scientists for Social and Environmental Responsibility, 2020-06-16 20:50:52.
This series of five Webinars by some of the authors of the interdisciplinary Gene Drive Report (2019) and were organised by four organisations of independent scientists: the European Network of Scientists for Social and Environmental Responsibility (ENSSER), Critical Scientists Switzerland (CSS), Vereinigung Deutscher Wissenschaftler (VDW), Sciences Citoyennes (SC). The series was aimed at a lay audience and were intended to address these questions. Does it really work? Is it being applied? What problems do gene drives address? What side effects can they have? Who has an interest in this? Should we do it? Are gene drives regulated by law? Are they a wise solution to these problems? Who decides?
Species Extinction & the Case for a Global Moratorium on Gene Drives
12454M. Imken, ARC, 2020-06-14 20:33:30.
One million species are currently threatened with extinction, and humanity faces the challenge of stopping the sixth mass extinction in the history of our planet. Yet a new technology called Gene Drive enables human beings to reprogram wild species by genetic engineering and to drive these species to self-destruction and extinction.
The need for new vector control approaches targeting outdoor biting anopheline malaria vector communities
12808S. Sougoufara, E. C. Ottih and F. Tripet, Parasites & Vectors, 13:15. 2020-06-10 19:48:24.
Since the implementation of Roll Back Malaria, the widespread use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) is thought to have played a major part in the decrease in mortality and morbidity achieved in malaria-endemic regions. In the past decade, resistance to major classes of insecticides recommended for public health has spread across many malaria vector populations. Increasingly, malaria vectors are also showing changes in vector behaviour in response to current indoor chemical vector control interventions. Changes in the time of biting and proportion of indoor biting of major vectors, as well as changes in the species composition of mosquito communities threaten the progress made to control malaria transmission. Outdoor biting mosquito populations contribute to malaria transmission in many parts of sub-Saharan Africa and pose new challenges as they cannot be reliably monitored or controlled using conventional tools. Here, we review existing and novel approaches that may be used to target outdoor communities of malaria vectors. We conclude that scalable tools designed specifically for the control and monitoring of outdoor biting and resting malaria vectors with increasingly complex and dynamic responses to intensifying malaria control interventions are urgently needed. These are crucial for integrated vector management programmes designed to challenge current and future vector populations.
Gene Drive: Can this be the Future of Agricultural Pest Management?
13156P. Mondal, U. Mohapatra and M. Ganguly, International Journal of Current Microbiology and Applied Sciences, 9. 2020-06-10 14:25:16.
A world free of hunger may be possible when the agricultural production exceeds the global demand for the food. In the era of increasing population, the need for increased food production can be attainable by managing the destructive pests of the agricultural and horticultural crops. The detrimental effects of the pesticides and the attitudes of society towards transgenic crops indicate the researchers to catch out Gene Drive as the substitute method for former methods of crop pest management. In this context, the present narration describes how the self-sustaining CRISPR-based gene drive technology will be the leading technique in the near future for agriculture pest management.
Jonathan Latham on Gene Drives and the Gates Foundation
12259James Corbett, The Corbett Report, 2020-06-09 18:04:09.
Jonathan Latham of Independent Science News joins us to discuss his 2017 article, “Gates Foundation Hired PR Firm to Manipulate UN Over Gene Drives.” We talk about gene drives, the dangers inherent in this technology, how the UN is involved, and why the Gates Foundation and DARPA are so interested in introducing genetic modifications into various species.
Fighting malaria with gene-drive technology
12417EarthWise, earthwise radio, 2020-06-08 20:03:15.
A team led by Imperial College London has created a genetic modification that distorts the sex ratio of a population of Anopheles gambiae mosquitoes using “gene drive” technology. The modification works by using a DNA-cutting enzyme to destroy the X chromosome during the production of sperm, which leads to predominantly male offspring, since females require two X chromosomes. The modification is coupled to a gene drive to allow it to spread through a population in a very effective way. A gene drive is a genetic engineering technology that propagates a particular modification by assuring that a specific form of a gene (or allele) will be transmitted with far more than the natural 50% probability.
Conservation implications of disease control
12540J. C. Buck, S. B. Weinstein, G. Titcomb and H. S. Young, Frontiers in Ecology and the Environment, 6. 2020-06-08 15:44:22.
Infectious diseases have indelibly altered human history and, in doing so, have shaped the ecology and conservation of the natural world. Attempts to control diseases often result in adverse environmental impacts, including habitat degradation and unintended outcomes such as effects on non-target species. However, in instances where the most effective strategy is to physically avoid specific species or habitats, disease can also provide critical de facto conservation benefits to organisms and ecosystems. Increasingly, new genome-editing technologies offer the potential to eradicate long-term health scourges, which disproportionately affect people in developing countries. It will be critical to incorporate an understanding of the ecological consequences of disease control - including those mediated by changes in human behavior - into management strategies, and to do so without propagating environmental injustice. In this way, scientists, resource managers, and health practitioners can help to ensure that gains for human health do not result in losses for the natural world.
Mosquitoes engineered to resist the malaria parasite
12440Anonymous, Lab+Life Scientist, 2020-06-07 20:22:39.
Anopheles mosquitoes that have been genetically engineered with multiple antimalaria molecules, acting at different stages of the malaria life cycle, are strongly resistant to the parasite that causes malaria and are unlikely to lose that resistance quickly.
Motivations and expectations driving community participation in entomological research projects: Target Malaria as a case study in Bana, Western Burkina Faso
12435N. Barry, P. Toé, L. Pare Toe, J. Lezaun, M. Drabo, R. K. Dabiré and A. Diabate, Malaria Journal, 19:199. 2020-06-05 20:15:19.
Most field entomology research projects require active participation by local community members. Since 2012, Target Malaria, a not-for-profit research consortium, has been working with residents in the village of Bana, in Western Burkina Faso, in various studies involving mosquito collections, releases and recaptures. The long-term goal of this work is to develop innovative solutions to combat malaria in Africa with the help of mosquito modification technologies. Since the start of the project, Bana residents have played an important role in research activities, yet the motivations and expectations that drive their participation remain under-investigated. This study examines the factors that motivate some members of the local community to contribute to the implementation of Target Malaria’s activities, and, more broadly, explores the reasons that animate citizen participation in entomological research work in malaria-endemic regions.
Gene drives: benefits, risks, and possible applications
12414A. Deplazes-Zemp, U. Grossniklaus, F. Lefort, P. Müller, J. Romeis, A. Rüegsegger, N. Schoenenberger and E. Spehn, Swiss Academies Factsheets, 15. 2020-06-05 19:48:13.
Gene drives are genetic elements that skew the pattern of inheritance of a given characteristic in sexually reproducing organisms. They can be used to spread a characteristic that can alter or even reduce the numbers of individuals in wild populations of a certain species. As they spread by being inherited from one generation to the next, they could persist in populations long-term. The spreading property of gene drives could be a source of great potential in areas as diverse as the control of disease vectors, invasive species, agricultural pests and predators of endangered species. However, the same property may make containment challenging and therefore may also pose novel environmental risks. The evaluation, distribution of risks and benefits and the fact that gene drives may be seen as a particularly profound interference with nature raises further novel ethical considerations.
Can CRISPR gene drive work in pest and beneficial haplodiploid species?
12389J. Li, O. Aidlin Harari, A.-L. Doss, L. L. Walling, P. W. Atkinson, S. Morin and B. E. Tabashnik, Evolutionary Applications, 2020-06-03 18:14:33.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known about CRISPR gene drive in haplodiploids, despite their immense global impacts as pollinators, pests, natural enemies of pests, and invasive species in native habitats. Here we analyze mathematical models demonstrating that, in principle, CRISPR homing gene drive can work in haplodiploids, as well as at sex-linked loci in diploids. However, relative to diploids, conditions favoring the spread of alleles deleterious to haplodiploid pests by CRISPR gene drive are narrower, the spread is slower, and resistance to the drive evolves faster. By contrast, the spread of alleles that impose little fitness cost or boost fitness was not greatly hindered in haplodiploids relative to diploids. Therefore, altering traits to minimize damage caused by harmful haplodiploids, such as interfering with transmission of plant pathogens, may be more likely to succeed than control efforts based on introducing traits that reduce pest fitness. Enhancing fitness of beneficial haplodiploids with CRISPR gene drive is also promising.
Islands as Laboratories: Indigenous Knowledge and Gene Drives in the Pacific
12391R. I. Taitingfong, Human Biology, 91:179-188. 2020-06-01 18:19:55.
This article argues that the genetic engineering technology known as gene drive must be evaluated in the context of the historic and ongoing impacts of settler colonialism and military experimentation on indigenous lands and peoples. After defining gene drive and previewing some of the key ethical issues related to its use, the author compares the language used to justify Cold War–era nuclear testing in the Pacific with contemporary scholarship framing islands as ideal test sites for gene drive–modified organisms. In both cases, perceptions of islands as remote and isolated are mobilized to warrant their treatment as sites of experimentation for emerging technologies. Though gene drive may offer valuable interventions into issues affecting island communities (e.g., vector-borne disease and invasive species management), proposals to conduct the first open trials of gene drive on islands are complicit in a long history of injustice that has treated islands (and their residents) as dispensable to the risks and unintended consequences associated with experimentation. This article contends that ethical gene drive research cannot be achieved without the inclusion of indigenous peoples as key stakeholders and provides three recommendations to guide community engagement involving indigenous communities: centering indigenous self-determination, replacing the deficit model of engagement with a truly participatory model, and integrating indigenous knowledge and values in the research and decision-making processes related to gene drive.
Position Paper on Integrated Vector Management: Strengthening AU Members’ Regulatory Capacities for Responsible Research Towards Elimination of Malaria in Africa
12743African Union Development Agency - NEPAD, AUDA-NEPAD, 2020-06-01 13:48:16.
Africa continues to bear a heavy brunt of the malaria which is a disease transmitted by the female Anopheles mosquito. Thousands of lives, mostly of young children, are lost every year; which undermines efforts deployed at various levels for increased life expectancy and improved wellbeing for the socio-economic transformation of the continent. Accelerated changes and complementary tools are urgently needed to ensure effective elimination of malaria on the continent. Genetic engineering has been identified as one of such promising tools when applied to mosquito populations to reduce the transmission of the malaria parasite. The African Union Development Agency – NEPAD (AUDA-NEPAD), based on recommendations from the African Union High-Level Panel on Emerging Technologies (APET), continues to provide African Union Members States with the necessary support to ensure that research on and development of new genetically-based vector control tools are conducted in a responsible manner and in full compliance with safety requirements for human health and the environment for the benefit of African communities.
Engineered Gene Drives for Pest Management
25478G. Miglani, Biotechnology for Plant Disease Diagnosis and Management, 2020-06-01 09:06:32.
Genes in sexually reproducing organisms normally have, on average, a 50% chance of being inherited, but some genes have a higher chance of being inherited. These genes can increase in relative frequency in a population even if they reduce the odds that each organism will reproduce. Aided by technological advances, scientists are investigating how populations might be altered by adding, disrupting, or editing genes or suppressed by propagating traits that reduce reproductive capacity. Due to the discovery of gene-drive systems in insects and with the development of gene-drive technology using engineered site-specific nucleases, the last couple of years have seen a profound rise in excitement about the many possible uses of gene drive systems (GDSs). GDSs are capable of altering the traits of wild populations and associated ecosystems. A gene drive biases the transmission of a particular allele of a gene such that it is inherited at a greater frequency than by random assortment. A consequence of gene drives is an increased frequency of specific genetic elements or alleles and their accelerated spread throughout populations over successive generations. Here we will first describe the discovery, characteristics, types and mechanisms of GDSs. Next we will deal with development of gene-drive technology and its applications with special reference to their use in pest management and progresses that have so far been made to apply gene-drive systems in this area of research followed by limitations, safety and regulatory aspects of this technology. Finally, we will take up some key questions and future prospects of this important but still under-refinement technology.
Bioengineering horizon scan 2020
12449L. Kemp, L. Adam, C. R. Boehm, R. Breitling, R. Casagrande, M. Dando, A. Djikeng, N. G. Evans, R. Hammond, K. Hills, L. A. Holt, T. Kuiken, A. Markotić, P. Millett, J. A. Napier, C. Nelson, S. S. ÓhÉigeartaigh, A. Osbourn, M. J. Palmer, N. J. Patron, E. P, eLife, 9:e54489. 2020-05-29 20:28:54.
Horizon scanning is intended to identify the opportunities and threats associated with technological, regulatory and social change. In 2017 some of the present authors conducted a horizon scan for bioengineering (Wintle et al., 2017). Here we report the results of a new horizon scan that is based on inputs from a larger and more international group of 38 participants. The final list of 20 issues includes topics spanning from the political (the regulation of genomic data, increased philanthropic funding and malicious uses of neurochemicals) to the environmental (crops for changing climates and agricultural gene drives). The early identification of such issues is relevant to researchers, policy-makers and the wider public.
Simulation models from: Can CRISPER-mediated gene drive work in pest and beneficial haplodiploid species?
11968J. Li and B. Tabashnik, Dryad, 2020-05-26 18:17:03.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known about CRISPR gene drive in haplodiploids, despite their immense global impacts as pollinators, pests, natural enemies of pests, and invasive species in native habitats. Here we analyze mathematical models demonstrating that, in principle, CRISPR homing gene drive can work in haplodiploids, as well as at sex-linked loci in diploids. However, relative to diploids, conditions favoring the spread of alleles deleterious to haplodiploid pests by CRISPR gene drive are narrower, the spread is slower, and resistance to the drive evolves faster. By contrast, the spread of alleles that impose little fitness cost or boost fitness was not greatly hindered in haplodiploids relative to diploids. Therefore, altering traits to minimize damage caused by harmful haplodiploids, such as interfering with transmission of plant pathogens, may be more likely to succeed than control efforts based on introducing traits that reduce pest fitness. Enhancing fitness of beneficial haplodiploids with CRISPR gene drive is also promising.
New study highlights success of gene drive technology with preventing mosquito-spread diseases
12401A. Meckler-Pacheco, The California Aggie, 2020-05-25 18:47:25.
For the past 30 years, researchers have studied the usage of gene drive technology to stop the spread of malaria. The idea is to create genetically engineered mosquitoes (GEM) that are either resistant to carrying the malaria parasite or that fail to reproduce, which would result in the reduction of the mosquito population. The gene drive technology relies on the use of the Cas-9 enzyme, which ensures the passing of the new modified genes onto offspring in the introduced population.
Genetic Biocontrol for Invasive Species
11964J. L. Teem, L. Alphey, S. Descamps, M. P. Edgington, O. Edwards, N. Gemmell, T. Harvey-Samuel, R. L. Melnick, K. P. Oh, A. J. Piaggio, J. R. Saah, D. Schill, P. Thomas, T. Smith and A. Roberts, Frontiers in Bioengineering and Biotechnology, 8:452. 2020-05-25 18:12:26.
Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries.
Gene Drives: Pursuing opportunities, minimizing risk
11966K. L. Warmbrod, A. Kobokovich, R. West, G. Ray, M. Trotochaud and M. Montague, Center for Health Security, 2020-05-18 18:14:50.
This study analyzed the current state of gene drive technologies, the ways in which they might be deployed in the field, and the state of regulatory policy governing their development.
Le forçage génétique (gène drive) et ses applications
18210V. Courtier-Orgogozo, Bulletin de l'Académie Vétérinaire de France, 172:94-98. 2020-05-18 15:11:30.
Gene drive is a new genetic engineering technology that has been developed over the past five years and that allows genetic modifications to spread rapidly in natural populations. Potential applications are numerous, for public health issues, agriculture and conservation biology. This article presents the current developments in this biotechnology, as well as the issues and risks associated with it.
Hope rises as scientists eliminate malaria mosquitoes
11953A. Adeyemi, New Telegraph, 2020-05-14 17:57:14.
A team of researchers led by Imperial College London have spread a genetic modification that distorted the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology. According to the results of their study published yesterday in ‘Nature Biotechnology,’ the modification they initiated in the laboratory created more male offspring that was able to eliminate populations of malaria mosquitoes in the lab experiments.
Malaria mosquitoes eliminated in lab by creating all-male offsprings
11945Aishwarya, Inshorts, 2020-05-13 17:53:53.
Imperial College London-led team used 'gene drive' technology to spread genetic modification that distorted sex ratio through caged breed of malaria mosquitoes. This caused mosquitoes to produce more male offspring, eventually leading to no female birth. The study suggested such mosquitoes carrying a sex-distorter gene drive could help spread male bias within local malaria-carrying populations.
Researchers use “gene drive” technology to eliminate malaria mosquitoes in lab experiments
11619J. Ives, News Medical Life Sciences, 2020-05-13 16:15:18.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using 'gene drive' technology.
Genetically-manipulated male mosquitoes could eliminate females
11617B. Coxworth, New Atlas, 2020-05-13 16:13:30.
Several years ago, we heard how scientists were looking at eradicating malaria-carrying mosquitoes by making the females infertile. Now they're going a step further, by eliminating the females altogether.
Researchers discover way to eliminate malaria carrying mosquitoes
11615S. Digon, International Business Times, 2020-05-13 16:12:04.
Researchers from the Imperial College London have come up with a genetic modification that will pave the way for the elimination of malaria mosquitoes. Scientists say that the alteration distorts the sex ratio of caged Anopheles gambiae mosquitoes using what they call a ‘gene drive’ technology.
Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations
11548H. M. Sánchez C, J. B. Bennett, S. L. Wu, G. Rašić, O. S. Akbari and J. M. Marshall, BMC Biology, 18:50. 2020-05-12 14:50:48.
Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems—reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL—to explore their ability to be confined and remediated.
Public opinion on gene editing
11613P. Thomas, The Ecologist, 2020-05-11 16:10:29.
What does the public think of genetic engineering in food and farming? Is there more acceptance, or less, these days? Have the issues changed over time, or is it just more of the same? How well informed do you believe you are? Beyond GM like you to participate in our survey to help us find out. While many people could be forgiven for thinking the issue of GMOs has gone away, the last few years have been a period of rapid developments in terms of new genetic engineering techniques.
The malaria mosquito is eliminated in the lab by creating a population of all males
11611NewsDesk, Instant, 2020-05-11 16:08:42.
A team led by Imperial College London disseminates genetic modification that distorts the sex ratio through the Anopheles gambiae mosquito population that is locked up using ‘gene drive’ technology.
Malaria mosquitoes eliminated in lab by creating all male populations
11609H. Dunning, Imperial College London, 2020-05-11 16:07:00.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology.
A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae
11463A. Simoni, A. M. Hammond, A. K. Beaghton, R. Galizi, C. Taxiarchi, K. Kyrou, D. Meacci, M. Gribble, G. Morselli, A. Burt, T. Nolan and A. Crisanti, Nature Biotechnology, 2020-05-11 15:15:55.
We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae.
Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
11465A. Hoermann, S. Tapanelli, P. Capriotti, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler, bioRxiv, 2020-05-10 15:19:12.
Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression.
Gene drive dynamics in natural populations: The importance of density-dependence, space and sex
11453S. Dhole, A. L. Lloyd and F. Gould, arXiv, arXiv:2005.01838. 2020-05-07 18:26:02.
Here we review how different forms of density-dependence, spatial heterogeneity and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.
The EU not ready for the release of Gene drive organisms into the environment.
11602Pensoft Publishers, ScienceDaily, 2020-05-07 15:59:25.
In their study, published in the open-access journal BioRisk, an international group of scientists led by Marion Dolezel from the Environment Agency Austria, discuss the potential risks and impacts on the environment.
Beyond limits – the pitfalls of global gene drives for environmental risk assessment in the European Union
11458M. Dolezel, C. Lüthi and H. Gaugitsch, BioRisk, 15:1-29. 2020-05-04 14:58:37.
We evaluate the novel features of GDOs and outline the resulting challenges for the environmental risk assessment.
The development of complex and controversial innovations. Genetically modified mosquitoes for malaria eradication
11431V. Cisnetto and J. Barlow, Research Policy, 49:103917. 2020-05-04 13:32:20.
e use a longitudinal process approach and qualitative system dynamics modelling to study the development of genetically modified (GM) mosquitoes for malaria eradication in an African country.
EFSA discusses risk assessment of gene drives
11606C. Then, Testbiotech, 2020-04-30 16:03:36.
The European Food Safety Authority (EFSA) carried out a public consultation on guidance for the risk assessment of so-called gene drives at the request of the EU Commission. At the same time, a new Testbiotech scientific paper was accepted after peer review. The paper shows that the EFSA concept is insufficient. To control the risks of gene drives, ‘cut-off criteria’ need to be defined to prevent the uncontrolled spread of genetically engineered organisms.
Gene drive outcomes not determined by genetic variation – A Podcast
11240Thomas Locke, Malaria Minute, 2020-04-29 17:23:49.
Gene drives are a system of genetic modification that use ‘molecular scissors’ to edit DNA sequences that self-perpetuate to ensure the rapid spread of mutation in a population. They offer new avenues for eradicating vector-borne diseases like malaria. They rely on the Cas9 system which works by recognising a specific 23-base pair stretch of DNA, assisted by a complementary RNA molecule which guides the enzyme and a donor DNA fragment that replaces the original DNA sequence. If there was genetic variation in the mosquito with respect to the RNA guide molecule used, however, it’s thought that such recognition would be less likely, meaning that the gene drive could fail. But a new study published this week suggests that this isn’t the case. Out of over 1,000 Anopheles mosquitoes analysed, around 90% had at least one target site for the Cas9 protein, suggesting that gene drives are still viable and not dependent on variation.
Alternative Techniques and Options for Risk Reduction of Gene Drives
11265Bernd Giese, Arnim von Gleich and Johannes L. Frieß, Gene Drives at Tipping Points, 2020-04-28 18:59:49.
In this chapter, we analyse and compare different types of gene drives as well as promising alternative approaches that may provide a reduced risk.
Limits of Knowledge and Tipping Points in the Risk Assessment of Gene Drive Organisms
11263Arnim von Gleich and Winfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:50:47.
New challengesTipping point in the risk assessment of genetically engineered (GE) organisms are expected to emerge in the context of so-called ‘gene drives’. Based on a review of findings from current knowledge of GE organisms, it is concluded that the risk assessment of gene drive organisms intended for release into the environment will inevitably suffer from major uncertainties, ‘unknowns’ and methodological problems: subsequent generations of GE organisms might show effects that were not observed or intended in the first generation. Unintended effects can, for example, emerge from interaction with genetic backgrounds within natural populations or be triggered by changing environmental conditions. Due to the increasing spatio-temporal complexity associated with the long-term persistence and propagation of GE organisms, risk assessment can no longer be expected to produce sufficiently reliable results. It has to be assumed that at a certain point in the dissolution of spatio-temporal boundariesa tipping point will be reached, that will make reliable risk assessment impossible. Moreover, methodological problems need to be overcome: the comparative approach that is the starting point for current European Food Safety Authority (EFSA)European Food Safety Authority (EFSA)’s environmental risk assessment might not be applicable due to the lack of suitable ‘comparators’. Despite increasing uncertainties, riskassessors and risk managers need to solve the problems of how to come to robust conclusions and make reliable decisions that take the precautionary principle(PP) into sufficient consideration. The introduction of a new step in the risk assessment of genetically engineered organisms has been suggested to solve these problems—which is the ‘spatio-temporal controllability’ and takes three criteria into account:(1)the biology of the target organisms,(2)their naturally occurring interactions with the environment (biotic and abiotic),(3)the intended biological characteristics (traitsTraits) of the GE organismsGenetically engineered organism.
Steps Towards a Precautionary Risk Governance of SPAGE Technologies Including Gene-Drives
11261Arnim von Gleich, Gene Drives at Tipping Points, 2020-04-28 18:44:32.
In view of the rapid dynamics of genetic engineering development (in particular regarding the ‘new gene-technologies’ gene editing, self-propagating artificial genetic elements (SPAGESelf-Propagating Artificial Genetic Elements (SPAGE)) and synthetic biology), the question is being intensively discussed whether the currently practiced risk governance is sufficient to guarantee the desired high level of health, consumer and environmental safety. Especially the extreme spatial and temporal environmental exposure due to released SPAGEs is identified as a problem because it leads to an enormous expansion of ignorance about possible situations and interactions. Therefore it requires measures based on the precautionary principle. Workable ways to integrate the precautionary principle into environmental risk assessment and risk regulation are being developed.
Model Concepts for Gene Drive Dynamics
11259Johnannes L. Frieß, Merle Preu and Broder Breckling, Gene Drives at Tipping Points, 2020-04-28 18:40:56.
The GeneTip project works on the conception and design modeling of population dynamics influenced by gene drives. In this pursuit, multiple different approaches and concepts have been developed to on one hand, be able to cover a broad perspective on the topic but on the other hand to also focus on different key aspects. In the following we present seven concepts based on different modeling approaches. In these model concepts our model organism is the olive fruit fly (Bactrocera oleae), which is a major pest species in agricultural olive production.
Case Study 2: Oilseed Rape (Brassica napus L.)
11257Johnannes L. Frieß, Broder Breckling, Kathrin Pascher and Windfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:36:22.
SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) (Self-Propagating Artificial Genetic Element) technologies allow for a proliferation of genetic information on the populationPopulation level at a higher rate than usual Mendelian inheritanceMendelian inheritance. Currently projected developments of SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) mainly aim at a reduction or suppressionSuppression of animal populationsPopulation which are considered to be harmful or undesirable (Oye et al. 2014). However, the application of SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) is not limited to animals only. In principle, also plant populationsPopulation can be targeted (National Academies of Sciences 2016). The GeneTip case study on oilseed rape (Brassica napus) is intended to assess, which interactions play a role in a plant-specific context to address relevant ecological interactions that need to be fully explored in order to estimate potential risksRisk.
Case Study 1: Olive Fruit Fly (Bactrocera oleae)
11255Merle Preu, Johannes L. Frieß, Broder Breckling and Winfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:31:15.
The olive fruit fly Bactrocera oleae is a phytophagous insect associated to olive trees (Olea europaea, Oleaceae). Its larvae monophagously feed on olive fruits, the fly is therefore considered the most severe pest of olive cultivation causing tremendous economic losses. The olive fly therefore poses a good example of a potential target organism in a European context. This case study revealed that uncertainties exist with regard to the dispersal capacity of gene drive-bearing olive flies, as well as concerning the high gene flow between different populations and most importantly with regard to the population bottlenecks that regularly occur in winter. These would significantly increase or decrease genetic variability between subpopulations and thereby severely jeopardize the intended outcome of any SPAGE-application.
Vulnerability Analysis of Ecological Systems
11253Carina R. Lalyer, Arnim von gleich, Bernd Giese, Gene Drives at Tipping Points, 2020-04-28 18:28:04.
Vulnerability analysis can be seen as the counterpart to technology characterization. Technology characterisation scrutinises the intervening technology. Vulnerability analyses potentially affected systems. That may be socio-ecological, socio-technical, socio-economic or other systems. In this chapter ecological systems are in focus.
Gene Drives Touching Tipping Points
11251Brodee Breckling, Arnim von Gleich,, Gene Drives at Tipping Points, 2020-04-28 18:24:58.
Tipping points and tipping elements, phase transitions and similar critical phenomena are widely discussed in scientific as well as socio-economic contexts as components to understand unforeseen far reaching changes and critical transitions from one stage into another in complex systems caused by small perturbations or gradual changes. For the risk assessment of self-propagating artificial genetic elements in self-sustaining population wild populationsof animals or plants, it is crucial to understand, where tipping elements could become relevant, how they could be anticipated and to what extent surprises and unexpected effects might occur.
Technology Characterisation
11249Johannes L. Frieß, Bernd Giese, Arnim von Gleich, Gene Drives at Tipping Point, 2020-04-28 18:21:27.
In recent years, innovation in genetic engineering brought forth a number of technologies to manipulate the fate of entire wild typeWild type populations. These technologies rely on the dissemination of synthetic genetic elements within a population of sexually reproducing species via the germline and are identified as Self-Propagating Artificial Genetic Elements (SPAGESelf-Propagating Artificial Genetic Elements (SPAGE)). Some secure their dissemination passively so that only offspring carrying the SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) will survive or be fertile. Others overcome the limitations of the Mendelian inheritance pattern by a distortion of allelic segregation or a fragmentation of chromosomes, resulting in e.g. an altered sex ratio. Genetic elements may also promote their preferred inheritance by a molecular mechanism. If a SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) overcomes the Mendelian pattern of inheritance and is thereby enabled to spread and distribute a novel traits throughout a population – even defying natural selection – it is called a gene drive. If organisms have a comparably short generation time, as e.g. insects, then already after a few months, a large part of the population could express a new property transmitted by the gene drive. In particular, very invasivegene drives may be able to impose properties on entire populations that otherwise could not spread.
Gene Drives at Tipping Points
11247Amin von Gleich and Winfried Schroder, Gene Drives at Tipping Points, 2020-04-28 18:14:49.
This open access book reports on a pilot project aiming at collecting information on the socio-ecological risks that could arise in the event of an uncontrolled spread of genetically engineered organisms into the environment. The researchers will, for instance, be taking a closer look at genetically engineered oilseed rape, genetically engineered olive flies as well as plants and animals with so-called gene drives. The book mainly adresses researchers.
GeneTip project results published in full
11604C. Then, Testbiotech, 2020-04-27 16:01:59.
The GeneTip research project was a joint enterprise carried out from 2017 until 2019 by the Universities of Bremen and Vechta, the University of Natural Resources and Life Sciences, Vienna and Testbiotech, Munich. The researchers focused on risks associated with the spread of newly designed genetically engineered organisms into the environment. In particular, the project examined plants and animals with a so-called gene drive. The results have now been published in full by the Springer Publishing Company in a book titled “Gene Drives at Tipping Points“ (open access).
Genetic Biocontrol – An Overview (video 13.13 min)
11398GeneConvene Global Collaborative, 2020-04-25 12:41:00.
This video explains what genetic biocontrol is and surveys various technologies that can be consider genetic biocontrol technologies. It offers a conceptual organization of the various technologies based on the potential of genetic biocontrol organisms to persist and spread in an environment. This video was produced by the GeneConvene Global Colaborative.
Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania
11461M. F. Finda, N. Christofides, J. Lezaun, B. Tarimo, P. Chaki, A. H. Kelly, N. Kapologwe, P. Kazyoba, B. Emidi and F. O. Okumu, Malaria Journal, 19:164. 2020-04-23 15:13:29.
Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania.
Pest control with genetically modified insects
11238myScience, myScience, 2020-04-21 17:18:07.
To control pests without pesticides, genetically modified organisms of the same species could be used. The latter carry a gene that is passed on with above-average frequency via sexual reproduction. This gene possesses traits that directly weaken the pest, or prevent pathogens from being transmitted. But how can the environmental impact of such gene-drive elements be recorded and assessed? Experts from Agroscope have authored a concept study on this topic.
Can we kill the dreaded mosquito? Do we even want to?
11228Stacey McKenna, Sierra, 2020-04-19 15:40:08.
As a major vector for disease, the mosquito has harmed more human beings than just about any other animal, and a changing climate is only boosting those numbers. As the range of disease-carrying species of mosquitoes expands, so does their ability to transmit the parasites and viruses that result in malaria, chikungunya, Zika, yellow fever, West Nile, and dengue fever. In 2018, the continental United States saw a 25 percent increase in severe, neuroinvasive cases of West Nile virus compared with a decade earlier. And over the past three decades, the CDC reports, the worldwide incidence of dengue fever has risen 30-fold.
Gene drives as a gene modification tool. A scientific overview.
11232Ashan Ali, TechnologyTimes, 2020-04-18 15:46:03.
We have heard a lot of genes and chromosomes. But we have not heard about gene drives. In this article, we are going to get an overview of gene drives. Gene Drive is basically a genetic engineering technique that helps in the accumulation and propagation of a particular set of traits throughout the population. Gene drives basically increase the chances of certain traits to pass on to the next generations. Gene Drives arise through various mechanisms. Gene-editing techniques like CRISPR have enabled the researchers to construct gene drives. Gene drives actually are an effective method of modifying specific populations and entire species.
Controversial ‘gene drive’ could disarm deadly wheat pathogen
11236Elizabeth Pennisi, Science, 2020-04-17 17:12:53.
The Fusarium fungus is the bane of every wheat farmer’s existence. Causing wheat scab—also known as head blight—it decimates harvests and contaminates grains with a toxin harmful to people and animals. Now, Australian researchers have come up with a new strategy to combat Fusarium graminearum, the most notorious wheat scab pathogen. In the lab, they have used a genome-altering technology called “gene drive” to get rid of the fungal genes that make this pest so toxic.
Genetic variation not an obstacle to gene drive strategy to control mosquitoes
11230University of California Davis, ScienceDaily, 2020-04-16 15:42:49.
New research from entomologists at UC Davis clears a potential obstacle to using CRISPR-Cas9 "gene drive" technology to control mosquito-borne diseases such as malaria, dengue fever, yellow fever and Zika.
Gene editing and the war against malaria
11226E. Bier and E. Sobber, American Scientist, 102:162. 2020-04-16 15:34:38.
Malaria is a devastating disease transmitted from person to person by mosquitoes. It kills more than 400,000 people per year, more than half of those deaths being children 5 years old or younger. CRISPR (clustered regularly interspaced short palindromic repeats) is a new gene-editing technology that acts like a pair of molecular scissors: It is used to “cut and paste” DNA sequences to alter gene function. In “Gene Editing and the War Against Malaria” (pages 162–169), Ethan Bier and Elliott Sober describe how biologists can now alter genes in a malaria-transmitting mosquito population by engineering a CRISPR gene drive, which mimics a natural evolutionary process. With this tool, a new gene can be inserted into the genome so that the alteration is rapidly passed down to successive sexually reproducing generations. Two gene-drive strategies have been found feasible: The first drives a local malaria-transmitting population to extinction; the second renders mosquitoes unable to transmit malaria, which breaks the malaria transmission cycle.
Report of the ad hoc technical expert group on risk assessment
16095Ad Hoc Technical Expert Group on Risk Assessment, Convention on Biological Diversity, 2020-04-15 15:54:41.
The Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol further decided to extend the Online Forum on Risk Assessment and Risk Management to assist the AHTEG and invited submissions of information relevant to the work of the online forum and the AHTEG from Parties, other Governments, and indigenous peoples and local communities. The AHTEG is to submit the outcomes of its work for consideration by the Subsidiary Body on Scientific, Technical and Technological Advice at its twenty-fourth meeting, prior to the tenth meeting of the Parties to the Protocol.
Development and testing of a novel killer–rescue self-limiting gene drive system in Drosophila melanogaster
11214S. H. Webster, M. R. Vella and M. J. Scott, Proceedings of the Royal Society B: Biological Sciences, 287:20192994. 2020-04-15 15:04:49.
Here we report the development and testing of a novel self-limiting gene drive system, Killer–Rescue (K–R), in Drosophila melanogaster. This system is composed of an autoregulated Gal4 Killer (K) and a Gal4-activated Gal80 Rescue (R). Overexpression of Gal4 is lethal, but in the presence of R activation of Gal80 leads to much lower levels of Gal4 and rescue of lethality. We demonstrate that with a single 2 : 1 engineered to wild-type release, K drives R through the population and after nine generations, more than 98% of the population carry R and less than 2% of the population are wild-type flies. We discuss how this simple K–R gene drive system may be readily adapted for population replacement in a human health pest, Aedes aegypti, or for population suppression in an agricultural pest, Drosophila suzukii.
Gene Drive Basics – Characteristics and Properties
11412GeneConvene Global Collaborative, 2020-04-15 14:11:41.
This short video covers the concept of 'drive strength', 'drive thresholds', 'spreading', 'resistance' and describes two strategies by which transmission advantages can be achieved. The video is intended to provide additional insights into the technology to enable and encourage thoughtful discussions.
Gene editing could fight malaria by causing only male mosquitos to be born
11958L. Dormehl, Digital Trends, 2020-04-14 18:01:16.
What’s the theoretically easiest way to ensure that a population of mosquitos is not able to sustain itself through breeding? Make sure that there aren’t enough females, of course. That’s the exploratory approach being pioneered by researchers at the U.K.’s Imperial College London, who have developed a way of distorting the sex ratio in species of Anopheles gambiae mosquitoes to ensure that offspring are predominantly male. Over a relatively short period of time, this causes the population of mosquitos to collapse — and, potentially, halts one of the main vectors for spreading diseases like malaria as a result.
GENE DRIVE ORGANISMS: Implications for the environment and nature conservation
16092M. Dolezel, S. Simon, M. Otto, M. Engelhard and W. Zughart, Umweltbundesamt, 2020-04-09 15:46:47.
Recent advances in biotechnology aim at the genetic modification of wild living populations. Some potential applications consider self-propagating genetic elements to generate gene drive organisms (GDOs), also for nature conservation. Due to the potential of GDOs to spread spatially and temporally unlimited, impacts on the environment and ecosystems may be irreversible and are difficult to predict. This technical report summarizes the status of gene drive applications currently discussed in the scientific literature. It outlines their potential implications for the environment and nature conservation and highlights challenges with respect to the environmental risk assessment and post-release monitoring of GDOs, in particular in a context of high complexity and uncertainty.
Spatio-temporal controllability and environmental risk assessment of genetically engineered gene drive organisms from the perspective of EU GMO Regulation
11208C. Then, K. Kawall and N. Valenzuela, Integrated Environmental Assessment and Management, 2020-04-06 14:38:52.
Gene drive organisms are a recent development created by using methods of genetic engineering; they inherit genetic constructs that are passed on to future generations with a higher probability than with Mendelian inheritance. There are some specific challenges inherent to the environmental risk assessment (ERA) of genetically engineered (GE) gene drive organisms, since subsequent generations of these GE organisms might show effects that were not observed or intended in the former generations. Unintended effects can emerge from interaction of the gene drive construct with the heterogeneous genetic background of natural populations and/or be triggered by changing environmental conditions. This is especially relevant in case of gene drives with invasive characteristics and typically takes dozens of generations to render the desired effect. Under these circumstances, ‘next generation effects’ can substantially increase the spatial and temporal complexity associated with a high level of uncertainty in ERA. To deal with these problems, we suggest the introduction of a new additional step in the ERA of GE gene drive organisms that takes three criteria into account: the biology of the target organisms, their naturally occurring interactions with the environment (biotic and abiotic) and their intended biological characteristics introduced by genetic engineering. These three criteria are merged to form an additional step in ERA, combining specific ‘knowns’ and integrating areas of 'known unknowns' and uncertainties, with the aim of assessing the spatio‐temporal controllability of GE gene drive organisms. The establishment of assessing spatio‐temporal controllability can be used to define so‐called ‘cut‐off’ criteria in the risk analysis of GE gene drive organisms: if it is likely that GE gene drive organisms escape spatio‐temporal controllability, the risk assessment cannot be sufficiently reliable because it is not conclusive. Under such circumstances, the environmental release of the GE gene drive organisms would not be compatible with the precautionary principle (PP).
Natural gene drives offer potential pathogen control strategies in plants
11206D. M. Gardiner, A. Rusu, L. Barrett, G. C. Hunter and K. Kazan, bioRxiv, 2020-04-06 14:21:48.
Globally, fungal pathogens cause enormous crop losses and current control practices are not always effective, economical or environmentally sustainable. Tools enabling genetic management of wild pathogen populations could potentially solve many problems associated with plant diseases. A natural gene drive from a heterologous species can be used in the globally important cereal pathogen, Fusarium graminearum, to remove pathogenic traits from contained populations of the fungus. The gene drive element became fixed in a freely crossing populations in only three generations. Repeat induce point mutation, a natural genome defence mechanism in fungi, may be useful to recall the gene drive following release, should a failsafe mechanism be required. We propose that gene drive technology is a potential tool to control plant pathogens.
Engineering multiple species-like genetic incompatibilities in insects
12543M. Maselko, N. Feltman, A. Upadhyay, A. Hayward, S. Das, N. Myslicki, A. J. Peterson, M. B. O’Connor and M. J. Smanski, bioRxiv, 2020-04-05 17:32:23.
Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such control would provide safe biocontainment of transgenes and gene drives. Natural speciation can be driven by pre-zygotic barriers that prevent fertilization or by post-zygotic genetic incompatibilities that render the hybrid progeny inviable or sterile. Here we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. Our system couples a dominant lethal transgene with a recessive resistance allele. EGI strains that are homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. We show that EGI genotypes can be tuned to cause hybrid lethality at different developmental life-stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. Our approach to create EGI organisms is simple, robust, and functional in multiple sexually reproducing organisms.
Gene drives could stop the world’s oldest problems
11224Chloe Willianms, Inverse, 2020-04-01 15:31:23.
Kevin Esvelt worries more than the average scientist. It’s a consequence of having invented a technology powerful enough to alter an entire species. In 2013, Esvelt came up with the concept of CRISPR-based gene drive. The technology uses CRISPR, a gene editing tool, to hack the laws of inheritance: It allows scientists to genetically modify a few individuals that then spread a modified gene throughout an entire population, and eventually, every population around the world.
Auditing preparedness for vector control field studies
11210C. M. Collins and M. M. Quinlan, American Journal of Tropical Medicine and Hygiene, 102:707-710. 2020-04-01 14:52:00.
The value of baseline entomological data to any future area-wide release campaign relies on the application of consistent methods to produce results comparable across different times and places in a stepwise progression to larger releases. Traditionally, standard operating procedures (SOPs) and operational plans support this consistency and, thus, the validity of emergent data. When release plans include transgenic mosquitoes for vector control or other novel beneficial insects, additional factors come into play such as biosafety permits, stakeholder acceptance, and ethics approval, which require even greater coordination and thoroughness. An audit approach was developed to verify the correct use of SOPs and appropriate performance of tasks during mosquito mark, release, recapture (MRR) studies. Audit questions matched SOPs, permit terms and conditions, and other key criteria, and can be used to support subsequent “spot check” verification by field teams. An external team of auditors, however, was found to be effective for initial checks in this example before the use of a transgenic strain of laboratory mosquitoes. We recommend similar approaches for field studies using release of novel beneficial insects, to ensure useful and valid data as an outcome and to support confidence in the rigor of the step-wise process.
Underdominance
11410GeneConvene Global Collaborative, 2020-04-01 13:58:43.
This video graphically explains the genetic concept of underdominance and illustrates how it can result in one allele replacing another allele in a population. While 'gene drive', underdominance is a genetic phenomenon that can be recreated using genetic technologies and might have applications as a genetic biocontrol strategy under some circumstances.
Engineering a minimal gene drive system for integral replacement in Drosophila melanogaster
25648A. Nash, Imperial College London, 2020-04-01 07:48:50.
Gene drives represent a powerful tool for the control of vector-borne diseases. By suppressing or replacing vector populations, laboratory studies have highlighted the potential for this group of tools to make a powerful impact on the burden of zoonotic disease. Current genetic drive systems have a number of limitations, namely their complexity, susceptibility to genetic resistance, and a high regulatory threshold. Here we suggest a novel design paradigm for the creation of replacement gene drives, which we have termed ‘Integral Replacement’. By splitting drive constructs, and integrating components into endogenous loci, we have aimed to engineer a minimal drive system, with low fitness cost, higher resilience to resistance alleles, and with greater flexibility for field testing. In so doing we have generated a model that illustrates increases in efficacy versus existing drive systems, and expanded on work performed on intronic gRNA cassettes. We subsequently were able to build prototype Integral Gene Drive (IGD) components, and demonstrate their efficacy using the model organism Drosophila melanogaster, providing evidence for an initial proof-of-principle for this novel design paradigm.
Development of control and sterilization technology for bluegill by genome editing
20100M. A. Madsen, Nippon Suisan Gakkaishi, 86:100-100. 2020-03-31 09:55:36.
This article is in Japanese
The value of existing regulatory frameworks for the environmental risk assessment of agricultural pest control using gene drive
8194J. Romeis, J. Collatz, D. C. M. Glandorf and M. B. Bonsall, Environmental Science & Policy, 108:19-36. 2020-03-27 20:20:04.
The application of (synthetic) gene drives is a powerful tool to control populations of insects that are agricultural pests, vectors of diseases, or a threat to biodiversity potentially leading to the local or global eradication of a species. The potential use of gene drive organisms has triggered a heated discussion regarding their environmental impacts and regulatory oversight. However, experience exists in assessing the environmental impacts of a number of established agricultural pest control methods that require the release of living organisms, that provide high levels of area-wide control and that might be irreversible. This includes classical biological control, the sterile insect technique, the incompatible insect technique that is based on the cytoplasmic incompatibility caused by Wolbachia endosymbionts, and genetically modified insects containing self-limiting traits. The different technologies are described, the regulatory practice and experience is summarized and pathways through which these control technologies could harm valued ecosystem services are presented. With a focus on the application of gene drives in agriculture, using the invasive Drosophila suzukii (Diptera: Drosophilidae) as a case study we then discuss to what extent the existing frameworks could assist the risk assessment of insects carrying gene drives. We suggest that drawing on existing practices, experiences and legislative frameworks will provide a pragmatic and proportionate approach to evaluate the environmental risks of novel solutions based on gene drive technologies.
Strategies for Achieving Gene Drive – Gonotaxis
11408GeneConvene Global Collaborative, 2020-03-27 13:46:56.
This video explains how there are three strategies for achieving gene drive and focuses on one, gonotaxis. Gonotaxis is explained and illustrated. While well-described in various plants and animals, gene drive researchers and technology developers have not recreated gonotaxis using transgenic approaches.
‘Gene Drive’ to curb malaria raises ethical questions as well
11220Gyanedra Nath Mitra, The Pioneer, 2020-03-25 15:23:14.
A new technology ‘Gene Drive’ for mosquito control is currently confined to the laboratory since it raises an ethical question, if such a technology could in future be misused to the detriment of humanity.
Strategies for Achieving Gene Drive – Interference
11406GeneConvene Global Collaborative, 2020-03-25 13:20:48.
This short video explains how there are essentially three genetic strategies for achieve 'drive' or 'gene drive'. This video focuses on the strategy of interference in which a genetic element achieves a transmission advantage or drives by disrupting the development of cells that do not carry the gene drive. This is a well documented strategy found in nature.
Strategies for Achieving Gene Drive – Over-Replication
11404GeneConvene Global Collaborative, 2020-03-24 13:10:14.
This short video explains how there are essentially three genetic strategies for achieve 'drive' or 'gene drive'. This video focuses on Over-Replication, a very common strategy associated wtih different types of genetic elements found in nature that 'drive'. This strategy is also used by researchers and developers to assemble transgenes that drive when introduced into the genome of an organism.
Can a population targeted by a CRISPR-based homing gene drive be rescued?
11269N. O. Rode, V. Courtier-Orgogozo and F. Débarre, bioRxiv, 2020.03.17.995829. 2020-03-20 19:12:23.
CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations through the release of individuals carrying an engineered piece of DNA that can be inherited by all their progeny. Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals carrying a brake construct that targets and inactivates the drive allele but leaves the wild-type allele unaffected. Here we develop models to investigate the efficiency of such brakes. We consider a variable population size and use a combination of analytical and numerical methods to determine the conditions where a brake can prevent the extinction of a population targeted by an eradication drive. We find that a brake is not guaranteed to prevent eradication and that characteristics of both the brake and the drive affect the likelihood of recovering the wild-type population. In particular, brakes that restore fitness are more efficient than brakes that do not. Our model also suggests that threshold-dependent drives (drives that can spread only when introduced above a threshold) are more amenable to control with a brake than drives that can spread from an arbitrary low introduction frequency (threshold-independent drives). Based on our results, we provide practical recommendations and discuss safety issues.Article summary for Issue Highlights Homing gene drive is a new genetic control technology that aims to spread a genetically engineered DNA construct within natural populations even when it impairs fitness. In case of unanticipated damages, it has been proposed to stop homing gene drives by releasing individuals carrying a gene-drive brake; however, the efficiency of such brakes has been little studied. The authors develop a model to investigate the dynamics of a population targeted by a homing drive in absence or in presence of brake. The model provides insights for the design of more efficient brakes and safer gene drives.CRISPRClustered Regularly Interspaced Short Palindromic Repeats
Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs
7962S. E. Champer, S. Y. Oh, C. Liu, Z. Wen, A. G. Clark, P. W. Messer and J. Champer, Science Advances, 6:eaaz0525. 2020-03-16 14:22:56.
The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives. One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present. Here, we develop a model of homing mechanisms parameterized by experimental studies. Our model incorporates several factors affecting drives with multiple gRNAs, including timing of cleavage, reduction in homology-directed repair efficiency due to imperfect homology, Cas9 activity saturation, gRNA activity level variance, and incomplete homology-directed repair. We find that homing drives have an optimal number of gRNAs, usually between two and eight, depending on the specific drive type and performance parameters. These results contradict the notion that resistance rates can be reduced to arbitrarily low levels by gRNA multiplexing and highlight the need for combined approaches to counter resistance evolution in CRISPR homing drives.
Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologies
11201Marino, N. D., Pinilla-Redondo, R. , Csorgo, B., Bondy-Denomy, J., Nature Methods, 2020-03-16 13:52:42.
Clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes, a diverse family of prokaryotic adaptive immune systems, have emerged as a biotechnological tool and therapeutic. The discovery of protein inhibitors of CRISPR-Cas systems, called anti-CRISPR (Acr) proteins, enables the development of more controllable and precise CRISPR-Cas tools. Here we discuss applications of Acr proteins for post-translational control of CRISPR-Cas systems in prokaryotic and mammalian cells, organisms and ecosystems. This Review highlights recent discoveries and applications of anti-CRISPR (Acr) proteins that enable the regulation of CRISPR-Cas technology.
Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes
14309H. Schmidt, T. C. Collier, M. J. Hanemaaijer, P. D. Houston, Y. Lee and G. C. Lanzaro, Nature Communications, 11. 2020-03-16 12:39:04.
ere we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that similar to 90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of >= 1.0%.
The risks of using gene drives to get rid of ‘pesky species’
8176R. Lewis, Genetic Literacy Project, 2020-03-13 19:45:32.
The mammals of New Zealand have long posed a threat to native species. The Predator Free 2050 program is an effort to rid the island of these invaders – including using the tools of CRISPR-based genome editing to create a gene drive to jumpstart extinctions. It’s a very bad idea.
A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters
7973B. Fasulo, A. Meccariello, M. Morgan, C. Borufka, P. A. Papathanos and N. Windbichler, PLOS Genetics, 16:e1008647. 2020-03-13 15:02:19.
Author summary Harmful insect populations can be eliminated for a lack of females if they are made to produce mostly male offspring. There are genes that occur naturally that make males produce mostly sons and, although we don’t know exactly how they work, this appears to coincide with damage to the X-chromosome during the production of sperm. Recently, we showed in a mosquito species that such sex-biasing genes could also be constructed artificially from first principles. To better understand if this works in other species too, we designed and built male-biasing genes of two types in the fruit fly and determined what is needed to for a shift towards males. We show how different ways of cutting the X-chromosome DNA at different times with CRISPR, results in distinct outcomes and started to ask what cellular processes are involved in this. These models will help us to design such genes for the control of insect species that transmit disease or threaten crops.
Performance analysis of novel toxin-antidote CRISPR gene drive systems
7969J. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer, BMC Biology, 18:27. 2020-03-12 14:48:01.
CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. However, current homing-type drives have two potential shortcomings. First, they can be thwarted by the rapid evolution of resistance. Second, they lack any mechanism for confinement to a specific target population. In this study, we conduct a comprehensive performance assessment of several new types of CRISPR-based gene drive systems employing toxin-antidote (TA) principles, which should be less prone to resistance and allow for the confinement of drives to a target population due to invasion frequency thresholds.
Stakeholder workshop “Problem formulation for the environmental risk assessment of gene drive modified insects” (15 May 2019, Brussels)
8192European Food Safety, A., Devos, Y., Gallani, B. & Firbank, L. G, A. European Food Safety, Y. Devos, B. Gallani and L. G. Firbank, 17:1819E. 2020-03-09 20:12:26.
Recent advances in molecular and synthetic biology are enabling the engineering of gene drives that spread genes of interest through interbreeding populations at a frequency greater than the rate expected by simple Mendelian inheritance. At present, insects represent the most likely cases of gene drive modified organisms for deliberate release into the environment. Through an open workshop, the European Food Safety Authority (EFSA) aimed to engage with stakeholders to discuss potential environmental risks associated with the deliberate release into the environment of gene drive modified insects. Workshop participants were invited to contribute to an example problem formulation to: (1) identify relevant broad protection goals and make them operational for use in environmental risk assessment; (2) formally devise examples of plausible pathways to harm that describe how the deployment of gene drive modified insects could be harmful; (3) formulate example risk hypotheses about the likelihood and severity of such events; (4) identify possible information that would be useful to test these risk hypotheses; and (5) identify how to acquire new data for hypothesis testing when existing information is deemed insufficient for regulatory decision-making. The problem formulation exercise was run for two hypothetical case studies (i.e. self-sustaining low threshold gene drives to control disease-spreading mosquitoes (Aedes albopictus, the Asian tiger mosquito) and agricultural pests (Drosophila suzukii, the spotted-wing Drosophila)). Points raised by the workshop participants reveal different often contrasting opinions/perspectives toward gene drive and their risk assessment. Overall, there was agreement that the problem formulation process is fit-for-purpose for the environmental risk assessment of gene drive modified insects, but it was acknowledged that practical challenges may be encountered. Points raised by the workshop participants, on defining protection goals, formulating specific pathways to harm and on structuring risks, have been considered by EFSA's Panel on genetically modified organisms during its deliberations.
NZ’s great pest-free quest: can we get there?
8181J. Morton, NZ Herald, 2020-03-09 19:58:28.
The Government has unveiled how it plans to rid New Zealand of possums, rats and stoats by 2050 – but there's no specific mention of contentious gene-editing technology that many scientists say will be needed. The Predator Free 2050 strategy, being formally launched this morning by Conservation Minister Eugenie Sage, sets out a basic structure for the ambitious mission, while an accompanying action plan focuses on work for the next five years. The 2050 goal, first announced by the previous National-led government in 2016, forms one of New Zealand's principal efforts to turn the tide on pests killing some 25 million native birds each year. The just-released strategy focused on three steps: mobilising groups and setting up collaborations around the country; developing "new and transformational tools and techniques" that'll be required to eradicate the pests; and then applying these at scale across the countryside.
Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing
7971S. L. James, J. M. Marshall, G. K. Christophides, F. O. Okumu and T. Nolan, Vector Borne and Zoonotic Diseases, 20:237. 2020-03-09 14:54:00.
Mosquitoes containing gene drive systems are being developed as complementary tools to prevent transmission of malaria and other mosquito-borne diseases. As with any new tool, decision makers and other stakeholders will need to balance risks (safety) and benefits (efficacy) when considering the rationale for testing and deploying gene drive-modified mosquito products. Developers will benefit from standards for judging whether an investigational gene drive product meets acceptability criteria for advancing to field trials. Such standards may be formalized as preferred product characteristics and target product profiles, which describe the desired attributes of the product category and of a particular product, respectively. This report summarizes discussions from two scientific workshops aimed at identifying efficacy and safety characteristics that must be minimally met for an investigational gene drive-modified mosquito product to be deemed viable to move from contained testing to field release and the data that will be needed to support an application for first field release.
Population-level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus
11212M. P. Edgington, T. Harvey-Samuel and L. Alphey, Evolutionary Applications, 10. 2020-03-06 14:52:40.
CRISPR-based gene drives bias inheritance in their favour by inducing double-stranded breaks (DSBs) at wild-type homologous loci and using the drive transgene as a repair template-converting drive heterozygotes into homozygotes. Recent studies have shown that alternate end-joining repair mechanisms produce cut-resistant alleles that rapidly induce drive failure. Multiplexing-simultaneously targeting multiple sites at the wild-type locus-is commonly assumed to overcome this issue since resistance would need to develop at all target sites for the system to fail. This may work for some population suppression drives targeting essential (e.g. viability or fertility) genes if careful design can ensure cut-resistant alleles themselves have low fitness. However, here, models are used to demonstrate that this approach will be ineffective when targeting neutral loci. We then go on to compare the performance of four alternative population-level multiplexing approaches with standard individual-level multiplexing. Two of these approaches have mechanisms preventing them from becoming linked, thus avoiding multiple simultaneous DSBs and giving a large improvement. Releasing multiple unlinked drives gives a modest improvement, while releasing multiple drives that may become linked over time produces a decrease in performance under the conditions tested here. Based on performance and technical feasibility, we then take one approach forward for further investigation, demonstrating its robustness to different performance parameters and its potential for controlling very large target populations.
What squirrels can teach us about why, when, and how to use gene drives
8184Rebecca Nesbit, synbiobeta, 2020-03-05 20:03:01.
As the last ice age drew to a close, red squirrels made Britain their home. They adapted to a changing landscape and thrived as the UK’s only squirrel species. That all changed in 1876 when grey squirrels were introduced to England from North America as an ornamental species in the grounds of stately homes.
A unifying approach to gene drive
7957P. Verma, R. Reeves and C. S. Gokhale, bioRxiv, 2020.02.28.970103. 2020-03-03 13:53:12.
Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The properties of gene drive constructs are diverse and depend on their molecular construction, and differential selection pressure they impose in the varied ecological situations they encounter. The extraordinary diversity of conceivable drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties. The sheer number of published manuscripts in this field, experimental and theoretical, is a testament to the possibilities presented by this technology. We evaluate and condense the essential synthetic drive mechanisms from a variety of studies and present a unified mathematical paradigm (and a user-friendly tool DrMxR - Drive Mixer) describing the properties of a wide variety of single construct gene drives (non-suppression). Within this common framework, we have been able to recapitulate key published results derived using bespoke modelling frameworks. Because a unified framework is employed, it is also possible to seamlessly explore the consequences of combining multiple drive approaches within a single construct. We provide a method for analytically assessing the measure of invasiveness of a drive construct. As opposed to typical studies of synthetic drives, we explore the resilience of such drives in a spatially explicit manner advancing the connection between realistic spatial dynamics and typical well-mixed populations. Besides a scientific advance, our results and the tools provided an intuitive and objective way for regulators, scientists and NGOs to evaluate the properties and robustness of proposed and future gene drive approaches.
Risk assessment challenges of synthetic gene drive organisms
12529E. Sirinathsinghji, TWN Biosafety Briefing, 2020-03-01 15:12:11.
Public health concerns over gene-drive mosquitoes: will future use of gene-drive snails for schistosomiasis control gain increased level of community acceptance?
7950D. O. Famakinde, Pathogens and Global Health, 2020-02-26 20:49:43.
With the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-based gene drive, present genetic research in schistosomiasis vector control envisages the breeding and release of transgenic schistosome-resistant (TSR) snail vectors to curb the spread of the disease. Although this approach is still in its infancy, studies focussing on production of genetically modified (GM) mosquitoes (including gene-drive mosquitoes) are well advanced and set the pace for other transgenic vector research. Unfortunately, as with other GM mosquitoes, open field release of gene-drive mosquitoes is currently challenged in part by some concerns such as gene drive failure and increased transmission potential for other mosquito-borne diseases among others, which might have adverse effects on human wellbeing. Therefore, not only should we learn from the GM mosquito protocols, frameworks and guidelines but also appraise the applicability of its current hurdles to other transgenic vector systems, such as the TSR snail approach. Placing these issues in a coherent comparative perspective, I argue that although the use of TSR snails may face similar technical, democratic and diplomatic challenges, some of the concerns over gene-drive mosquitoes may not apply to gene-drive snails, proposing a theory that community consent will be no harder and possibly easier to obtain for TSR snails than the experience with GM mosquitoes. In the future, these observations may help public health practitioners and policy makers in effective communication with communities on issues regarding the use of TSR snails to interrupt schistosomiasis transmission, especially in sub-Saharan Africa.
The Buzz About Genetically Modified Mosquitoes – a podcast
7932The Scientist Creative Services Team, The Scientist, podcast. 2020-02-26 18:17:44.
Mosquito-borne diseases afflict a large portion of the world. In this month’s episode, we consider genetic methods to eradicate diseases such as Zika fever, Dengue fever, and malaria. We spoke with Omar Akbari, professor of Cell and Developmental Biology at the University of California, San Diego, to learn more.
Understanding the Science of Gene Drive and the Potential for an Improved Crop Pest Control System in Nigeria
14882A. Isah and R. S. M. Gidado, OFAB Nigeria, 2020-02-26 15:52:39.
Several studies have shown that the Cas9-mediated gene drive technology is cheaper and will be easily affordable by the efficient Nigerian scientists to explore. The application of the gene drive technologies have many more controls over several other devastating insects in Nigeria and may be very necessary to adopt it to rescue our ailing food crop industry from the attack by destructive insect pest of crops.
Gene Drives: New and Improved
7945R. M. Friedman, J. M. Marshall and O. S. Akbari, Issues in Science and Technology, 36:1-7. 2020-02-18 20:39:12.
Our goal here is to describe the various options under development in nontechnical terms for a policy-making audience, review how far along each is, and examine the broader context of how this new suite of technologies compares with other available alternatives. Early engagement by the policy and regulatory communities will be of great help to product developers, and thus ultimately to society through better and more appropriate products. Our hope is that this improved understanding of what is in the development pipeline will enhance the dialogue between the policy community and developers.
Genome engineering in insects: focus on the CRISPR/Cas9 system
19405Hillary, V. Edwin Ceasar, Stanislaus Antony Ignacimuthu, S., Genome Engineering via CRISPR-Cas9 System, 2020-02-18 18:07:54.
Genome engineering is a precise tool used to alter the genome of desired organism. Zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR), and the CRISPR-associated RNA guided endonuclease Cas9 (CRISPR/Cas9) are the major genome engineering tools used in these days. CRISPR/Cas9 system has redeemed the precise genome engineering in different species including insects. This chapter covers the details on genome engineering studies reported in various insects including mosquitoes, butterflies, silkworm and fruit fly with a focus on CRISPR/Cas9 system. Many studies have been reported on application of ZFN, TALEN and CRISPR/Cas9 in insects. In recent years, many scientists have adopted CRISPR/Cas9 system for insect genome modification due to its affordability and quick designing of the constructs. We also discuss the details and applications of gene drive. Further studies with CRISPR/Cas9in insects will help researchers to find an effective strategy to combat the vector borne diseases spread by insects like mosquitoes.
Modeling the impacts of a simple meiotic gene drive on small, homeostatic populations
7956K. R. Pilkiewicz and M. L. Mayo, Physical Review E, 101:11. 2020-02-18 13:43:10.
Gene drives offer unprecedented control over the fate of natural ecosystems by leveraging non-Mendelian inheritance mechanisms to proliferate synthetic genes across wild populations. However, these benefits are offset by a need to avoid the potentially disastrous consequences of unintended ecological interactions. The efficacy of many gene-editing drives has been brought into question due to predictions that they will inevitably be thwarted by the emergence of drive-resistant mutations, but these predictions derive largely from models of large or infinite populations that cannot be driven to extinction faster than mutations can fixate. To address this issue, we characterize the impact of a simple, meiotic gene drive on a small, homeostatic population whose genotypic composition may vary due to the stochasticity inherent in natural mating events (e.g., partner choice, number of offspring) or the genetic inheritance process (e.g., mutation rate, gene drive fitness). To determine whether the ultimate genotypic fate of such a population is sensitive to such stochastic fluctuations, we compare the results of two dynamical models: a deterministic model that attempts to predict how the genetics of an average population evolve over successive generations, and an agent-based model that examines how stable these predictions are to fluctuations. We find that, even on average, our stochastic model makes qualitatively distinct predictions from those of the deterministic model, and we identify the source of these discrepancies as a dynamic instability that arises at short times, when genetic diversity is maximized as a consequence of the gene drive's rapid proliferation. While we ultimately conclude that extinction can only beat out the fixation of drive-resistant mutations over a limited region of parameter space, the reason for this is more complex than previously understood, which could open new avenues for engineered gene drives to circumvent this weakness.
What are gene drives about?
7377EFSAchannel, 2020-02-17 14:39:25.
EFSA expert Les Firbank, specialised in sustainable agriculture, talks about gene drives. Recent development in molecular biology are allowing scientists to engineer gene drives and use them to push desirable genes into target populations. How does that work? Learn more about this topic on in our new video.
Genetically engineered moths may save kale chips
7357C. Poku, BIOtechNOW, 2020-02-07 21:49:10.
Sea salt kale chips, bacon brussels sprouts, and buffalo cauliflower wings are under threat. Environmental activists will have you believe the biggest threat to our food system is pesticides. That’s not true, in fact, it’s insects—the very reason most pesticides are necessary. Insects are such a dangerous issue that Somalia recently declared a state of emergency as an “unprecedented” swarm of locusts is raising alarms about famine. Climate change has led to a rampant increase in bugs like locusts and moths, that threaten our food, and mosquitoes and ticks, that threaten people. A recent CNN article explains that diamondback moths are one of the most damaging insects because of their high reproduction rate and resistance to most insecticides.
Progress towards engineering gene drives for population control
7937R. R. Raban, J. M. Marshall and O. S. Akbari, The Journal of Experimental Biology, 223:jeb208181. 2020-02-07 20:21:50.
Vector-borne diseases, such as dengue, Zika and malaria, are a major cause of morbidity and mortality worldwide. These diseases have proven difficult to control and currently available management tools are insufficient to eliminate them in many regions. Gene drives have the potential to revolutionize vector-borne disease control. This suite of technologies has advanced rapidly in recent years as a result of the availability of new, more efficient gene editing technologies. Gene drives can favorably bias the inheritance of a linked disease-refractory gene, which could possibly be exploited (i) to generate a vector population incapable of transmitting disease or (ii) to disrupt an essential gene for viability or fertility, which could eventually eliminate a population. Importantly, gene drives vary in characteristics such as their transmission efficiency, confinability and reversibility, and their potential to develop resistance to the drive mechanism. Here, we discuss recent advancements in the gene drive field, and contrast the benefits and limitations of a variety of technologies, as well as approaches to overcome these limitations. We also discuss the current state of each gene drive technology and the technical considerations that need to be addressed on the pathway to field implementation. While there are still many obstacles to overcome, recent progress has brought us closer than ever before to genetic-based vector modification as a tool to support vector-borne disease elimination efforts worldwide.
Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination
7941P. Selvaraj, E. A. Wenger, D. Bridenbecker, N. Windbichler, J. R. Russell, J. Gerardin, C. A. Bever and M. Nikolov, bioRxiv, 2020.01.27.920421. 2020-02-06 20:32:18.
Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and many-to-many mappings of genotypes to phenotypes to investigate gene flow and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.Author summary Vector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.
Genetically engineered moths have been released into the wild to wipe out pests
7360K. Rogers, CNN, 2020-02-03 21:55:17.
Genetically modified diamondback moths designed to wipe out wild pest populations were released in fields for the first time in New York state. Diamondback moths are migratory pests found in the Americas, Europe, New Zealand and Southeast Asia, but especially in areas where crops can be grown yearround. In these parts -- where it's not too hot nor too cold -- are where diamondback moths cause the greatest problems, including billions of dollars in damages to cruciferous crops such as cabbage, broccoli, cauliflower and canola. They're one of the most damaging insects because of their high reproduction rate and resistance to most insecticides.
Engineering Bugs, Resurrecting Species: The Wild World of Synthetic Biology for Conservation
7242P. Rejcek, Singularity Hub, 2020-02-02 15:56:24.
Imagine a world where a mosquito bite is just an itchy annoyance. No malaria. No dengue fever. Last month, scientists announced they had taken one more step toward that vision. A paper in the journal PLOS Pathogens described how they synthetically engineered mosquitoes to stop the spread of dengue fever, a viral tropical disease that sickens as many as 100 million people each year. Now imagine genetically tweaking an invasive species of mosquito to save native Hawaiian birds from extinction, or transferring genes from one species of endangered chestnut tree to another to help the latter resist blight. Employing the same sort of genetic engineering used to make a plant-based burger bleed, scientists are beginning to explore the ways synthetic biology could help protect biodiversity and conserve species.
Gene technologies in weed management: a technical feasibility analysis
7948N. Kumaran, A. Choudhary, M. Legros, A. W. Sheppard, L. G. Barrett, D. M. Gardiner and S. Raghu, Current Opinion in Insect Science, 38:6-14. 2020-01-30 20:44:15.
With the advent of new genetic technologies such as gene silencing and gene drive, efforts to develop additional management tools for weed management is gaining significant momentum. These technologies promise novel ways to develop sustainable weed control options because gene silencing can switch-off genes mediating adaptation (e.g. growth, herbicide resistance), and gene drive can be used to spread modified traits and to engineer wild populations with reduced fitness. However, applying gene silencing and/or gene drive is expected to be inherently complex as their application is constrained by several methodological and technological difficulties. In this review we explore the challenges of these technologies, and discuss strategies and resources accessible to accelerate the development of gene-tech based tools for weed management. We also highlight how gene technologies can be integrated into existing management tactics such as classical biological control, and their possible interactions.
GMO diamondback moth shows promise as sustainable pest control tool in first ever open-field release
7262Cornell University, Genetic Literacy Project, 2020-01-29 16:35:41.
A newly published study reports a successful, first-ever open-field release of a self-limiting, genetically engineered diamondback moth, stating that it paves the way for an effective and sustainable approach to pest control. The diamondback moth, also known as Plutella xylostella, is highly damaging to brassica crops such as cabbage, broccoli, cauliflower and canola. This new strain of diamondback moth, developed by Oxitec Ltd, is modified to control pest diamondback moth in a targeted manner. The study showed the engineered strain had similar field behaviors to unmodified diamondback moths, with results offering promise for future protection of farmers’ brassica crops.
Male moths genetically modified to kill females released in the wild
7253M. Le Page, New Scientist, 2020-01-29 16:14:01.
Genetically modified male diamondback moths designed to wipe out pest populations have been released in New York state. The field trial shows that these GM moths, whose female offspring die soon after hatching, could help control this major crop pest. Oxitec, the British biotechnology company behind the trial, has already carried out field trials of this method for controlling mosquitoes that spread diseases such as dengue. However, the moth field trial is the first for a crop pest, the company says.
First Field Release of a Genetically Engineered, Self-Limiting Agricultural Pest Insect: Evaluating Its Potential for Future Crop Protection
7251A. M. Shelton, S. J. Long, A. S. Walker, M. Bolton, H. L. Collins, L. Revuelta, L. M. Johnson and N. I. Morrison, Frontiers in Bioengineering and Biotechnology, 7:1-15. 2020-01-29 16:10:21.
Alternative, biologically-based approaches for pest management are sorely needed and one approach is to use genetically engineered insects. Herein we describe a series of integrated field, laboratory and modeling studies with the diamondback moth, Plutella xylostella, a serious global pest of crucifers. A “self-limiting” strain of Plutella xylostella (OX4319L), genetically engineered to allow the production of male-only cohorts of moths for field releases, was developed as a novel approach to protect crucifer crops. Wild-type females that mate with these self-limiting males will not produce viable female progeny. Our previous greenhouse studies demonstrated that releases of OX4319L males lead to suppression of the target pest population and dilution of insecticide-resistance genes. We report results of the first open-field release of a non-irradiated, genetically engineered self-limiting strain of an agricultural pest insect. In a series of mark-release-recapture field studies with co-releases of adult OX4319L males and wild-type counterparts, the dispersal, persistence and field survival of each strain were measured in a 2.83 ha cabbage field. In most cases, no differences were detected in these parameters. Overall, 97.8% of the wild-type males and 95.4% of the OX4319L males recaptured dispersed <35 m from the release point. The predicted persistence did not differ between strains regardless of release rate. With 95% confidence, 75% of OX4319L males released at a rate of 1,500 could be expected to live between 3.5 and 5.4 days and 95% of these males could be expected to be detected within 25.8–34.9 m from the release point. Moth strain had no effect on field survival but release rate did. Collectively, these results suggest similar field behavior of OX4319L males compared to its wild-type counterpart. Laboratory studies revealed no differences in mating competitiveness or intrinsic growth rates between the strains and small differences in longevity. Using results from these studies, mathematical models were developed that indicate release of OX4319L males should offer efficacious pest management of P. xylostella. Further field studies are recommended to demonstrate the potential for this self-limiting P. xylostella to provide pest suppression and resistance management benefits, as was previously demonstrated in greenhouse studies.
Public Opinion Towards Gene Drive as a Pest Control Approach for Biodiversity Conservation and the Association of Underlying Worldviews
7348E. A. MacDonald, J. Balanovic, E. D. Edwards, W. Abrahamse, B. Frame, A. Greenaway, R. Kannemeyer, N. Kirk, F. Medvecky, T. L. Milfont, J. C. Russell and D. M. Tompkins, Environmental Communication-a Journal of Nature and Culture, 15:1-16. 2020-01-27 21:27:11.
Synthetic gene drive approaches are nascent technologies with potential applicability for pest control for conservation purposes. Responsible science mandates that society be engaged in a dialogue over new technology, particularly where there exist global ramifications as with gene drive. We hypothesize that public attitudes towards gene drive are not formed on scientific knowledge or demographics alone, but are heavily influenced by underlying worldviews, which encapsulate a broad and interactive system of attitudes, beliefs, and values. To test this, we conducted a national survey in New Zealand (n = 8199) and found that respondents clustered into four distinct segments with underlying worldviews, better able to explain attitudes toward gene drive than either the participants' scientific knowledge or other explanatory factors such demographics, political ideology or religiosity. We found that the use of gene drive for biodiversity conservation currently has moderate (32%) levels of support in New Zealand but that varied substantially across the four segments. Should gene drive become a technically viable approach for pest control, understanding the worldviews that shape public decision-making can guide a more empathetic engagement process and empower society to participate in informed decision-making about if and how gene drive should be used for conservation purposes.
Can CRISPR Save Tufty Fluffytail?
6954L. Tracey, JSTOR Daily, 2020-01-24 16:19:51.
The native red squirrel population in the UK has been decimated by the encroachment of its American cousin, an invasive species. Could a “gene drive” hel
Mosquitoes Genetically Engineered To Resist Dengue Fever
6951R. Bailey, reason, 2020-01-24 16:17:17.
Gene drives could spread this beneficial trait through wild mosquito populations.
Synthetically engineered mosquitos could neutralize dengue virus infection
6943L. Woolfe, Biotechniques, 2020-01-22 15:59:46.
Dengue virus infection can be severe and life threatening. New research has developed an improved approach to controlling this deadly infection.
Regulation of GM Organisms for Invasive Species Control
6701H. J. Mitchell and D. Bartsch, Frontiers in Bioengineering and Biotechnology, 7:1-11. 2020-01-21 18:17:37.
Invasive species can cause significant harm to the environment, agriculture, and human health, but there are often very limited tools available to control their populations. Gene drives (GD) have been proposed as a new tool which could be used to control or eliminate such species. Here, GD describes a variety of molecular biology applications which all enable the introduction of genetic elements at a higher than expected frequency. These elements can change the genotypes in target populations rapidly with consequences either for (intrinsic) fitness or host-parasite interaction, or both. Beneficial applications are foreseen for human and animal health, agriculture, or nature conservation. This rapidly developing technology is likely to have major impacts in the fight against various diseases, pests, and invasive species. The majority of GD applications involve genetic engineering and novel traits. Therefore, applicants and GMO regulators need to interact to achieve the benefits in innovation while cautiously avoiding unacceptable risks. The release into the environment may include transboundary movement and replacement of target populations, with potential impact on human/animal health and the environment. This article summarizes knowledge-based discussions to identify information gaps and analyzes scenarios for responsible introduction of GD organisms into the environment. It aims to connect the latest scientific developments with regulatory approaches and decision-making.
Davos 2020 World Economic Forum | When Humankind Overrides Evolution
6813M. Skipper, World Economic Forum, Davos 2020. 2020-01-21 15:32:08.
Advances in synthetic biology and other novel genetic procedures could resurrect extinct species or eliminate dangerous pests. What actions are needed now to ensure the ethical and responsible application of new genetic techniques?
Mosquitoes genetically modified to combat dengue
6740Downtoearth, Down To Earth, 2020-01-20 20:22:34.
For the first time mosquitoes have been engineered to fight all 4 known types of dengue
Genetically Modified Mosquitos Neutralize Dengue Virus
6737N. P. Dyal, Infectious Disease Advisor, 2020-01-20 18:53:09.
Researchers at the University of California San Diego have identified a target gene in mosquitos that renders the insects completely refractory to all 4 serotypes of the dengue virus and thus, incapable of transmitting the virus to humans, according to study results published in PLoS Pathogens
Irreversible ecosystem engineering with Gene Drive Organisms
8178Save Our Seeds, Save Our Seeds, 2020-01-18 19:56:07.
Gene drive technology is a particular application of the new genetic engineering tool CRISPR/Cas9. It is designed to genetically modify, replace or eradicate wild populations or entire species. So far it works in mosquitos, mice, flies, yeast and nematodes. But in principle it could be used to genetically modify any sexually reproducing organism. Gene drive organisms (GDOs) are meant to mate with their wild relatives and spread their engineered genes to ALL of their offspring. This forced inheritance pattern circumvents natures normal rules of inheritance. It triggers a genetic chain reaction in which the genetic engineering tool CRISPR/Cas9 and sometimes an additional new gene are passed on from generation to generation. Genetic changes induced by a gene drive can lead to sterility or the change of sex ratio of their descendants, leading to a crash in their population. First field trials in nature are foreseen for the near future.
Genetically modified mosquitoes resist all dengue viruses, researchers find
6709B. Burton, C|NET, 2020-01-17 18:24:25.
This new kind of mosquito can't spread any form of the deadly disease.
A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment
6668V. López Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz, Nature Communications, 11:352. 2020-01-17 18:00:23.
CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and supporting ecosystem conservation efforts. Current technologies raise safety concerns for unintended gene propagation. Herein, we address such concerns by splitting the drive components, Cas9 and gRNAs, into separate alleles to form a trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes. This dual-component configuration allows for combinatorial transgene optimization and increases safety by restricting escape concerns to experimentation windows. We employ the tGD and a small–molecule-controlled version to investigate the biology of component inheritance and resistant allele formation, and to study the effects of maternal inheritance and impaired homology on efficiency. Lastly, mathematical modeling of tGD spread within populations reveals potential advantages for improving current gene-drive technologies for field population modification.
Genetically engineered mosquitoes resist spreading any form of dengue
6734K. Servick, Science, 2020-01-16 18:50:53.
Recover from dengue once, and you’re not necessarily free and clear. The mosquito-borne disease marked by fever, rash, and debilitating pain results from any of four genetically distinct versions of the dengue virus. Previously infected people who get hit with a second of these “serotypes” can face more severe, even life-threatening symptoms. Now, by endowing a line of mosquitoes with an antibody against the virus, researchers have for the first time made insects that—at least in lab tests—appear unable to spread any form of the disease. In theory, these mosquitoes could be released into the wild to suppress the circulation of the virus.
Genetically engineered mosquitoes halt Dengue spread
6730L. Thomas, New Medical Life Sciences, 2020-01-16 18:44:27.
A new study published in the journal PLOS Pathogens in January 2020 reports the development of mosquitoes that have been genetically modified to resist infection by several types of the dengue virus. This is the first time ever that all types of the virus have been targeted by the engineering of the mosquito DNA. Covering all virus types is essential to achieve proper disease control.
Researchers Genetically Modify First Batch Of Mosquitoes Resistant To All Four Types Of Dengue
6725M. Dapcevich, IFL Science, 2020-01-16 18:39:05.
An international team of researchers have synthetically engineered a breed of mosquitos that are resistant to all four types of the dengue virus for the first time, a feat they say may someday suppress the disease and stop its transmission to humans.
Genetically engineered mosquitoes are immune to all strains of dengue virus for first time
6719G. Weule, ABC News Online, 2020-01-16 18:34:13.
Locked in a secure lab near Melbourne is the newest addition in the fight against dengue: genetically engineered mosquitoes that are resistant to all strains of the potentially deadly virus.
Mosquitoes resistant to all types of dengue virus engineered
6714N. Lavars, New Atlas, 2020-01-16 18:28:54.
Last year, scientists at Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO) made a big breakthrough, engineering mosquitoes that break the chain of Zika virus transmission. But they did so with multiple targets in mind, with the mosquito in question, Aedes aegypti, also acting as the number one disease vector for the dengue virus. The researchers have now added this arrow to the quiver of their genetically-modified mosquitoes, with hopes of tackling what they see as a global epidemic.
Broad dengue neutralization in mosquitoes expressing an engineered antibody
6706A. Buchman, S. Gamez, M. Li, I. Antoshechkin, H.-H. Li, H.-W. Wang, C.-H. Chen, M. J. Klein, J.-B. Duchemin, J. E. Crowe, Jr., P. N. Paradkar and O. S. Akbari, PLOS Pathogens, 16:e1008103. 2020-01-16 18:18:14.
Author summary With limited success of traditional vector control methods to curb dengue infections and more than half of the world’s population still at risk, there is a need for novel strategies to reduce its impact on public health. Recent advances in genetic technologies has allowed for precise modifications of mosquito genome to make them resistant to infections, thus breaking the transmission cycle. Here we generated engineered Ae. aegypti mosquitoes efficiently expressing a DENV-targeting single-chain variable fragment (scFv) derived from a previously characterized broadly neutralizing human antibody, which blocked infection and transmission in these mosquitoes. To our knowledge, this is the first example of an engineered transgene capable of rendering Ae. aegypti mosquitoes 100% refractory to all four serotypes of DENV. The engineered mosquitoes, in future, could easily be paired with a gene drive, capable of spreading the transgene throughout wild disease-transmitting mosquito populations and preventing further DENV transmission. Since a number of diverse and well-characterized antibodies exist against other arboviruses (eg chikungunya and Zika, this work also provides a proof-of-concept principle for developing similar genetic strategies for reducing the impact of these arboviruses.
Development of a confinable gene drive system in the human disease vector Aedes aegypti
6697M. Li, T. Yang, N. P. Kandul, M. Bui, S. Gamez, R. Raban, J. Bennett, H. M. Sánchez C, G. C. Lanzaro, H. Schmidt, Y. Lee, J. M. Marshall and O. S. Akbari, eLife, 9:e51701. 2020-01-16 18:07:34.
Aedes aegypti is the principal mosquito vector for many arboviruses that increasingly infect millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has sparked significant enthusiasm for genetic control of mosquitoes; however, no such system has been developed in Ae. aegypti. To fill this void, here we develop several CRISPR-based split gene drives for use in this vector. With cleavage rates up to 100% and transmission rates as high as 94%, mathematical models predict that these systems could spread anti-pathogen effector genes into wild populations in a safe, confinable and reversible manner appropriate for field trials and effective for controlling disease. These findings could expedite the development of effector-linked gene drives that could safely control wild populations of Ae. aegypti to combat local pathogen transmission.
The kill-switch for CRISPR that could make gene-editing safer
6647E. Dolgin, Nature, 577:308-310. 2020-01-15 20:32:43.
How anti-CRISPR proteins and other molecules could bolster biosecurity and improve medical treatments.
Antiviral effectors and gene drive strategies for mosquito population suppression or replacement to mitigate arbovirus transmission by Aedes aegypti
6634A. E. Williams, A. W. E. Franz, W. R. Reid and K. E. Olson, Insects, 11:1-18. 2020-01-12 20:05:33.
The mosquito vector Aedes aegypti transmits arthropod-borne viruses (arboviruses) of medical importance, including Zika, dengue, and yellow fever viruses. Controlling mosquito populations remains the method of choice to prevent disease transmission. Novel mosquito control strategies based on genetically manipulating mosquitoes are being developed as additional tools to combat arbovirus transmission. Genetic control of mosquitoes includes two basic strategies: population suppression and population replacement. The former aims to eliminate mosquito populations while the latter aims to replace wild populations with engineered, pathogen-resistant mosquitoes. In this review, we outline suppression strategies being applied in the field, as well as current antiviral effector genes that have been characterized and expressed in transgenic Ae. aegypti for population replacement. We discuss cutting-edge gene drive technologies that can be used to enhance the inheritance of effector genes, while highlighting the challenges and opportunities associated with gene drives. Finally, we present currently available models that can estimate mosquito release numbers and time to transgene fixation for several gene drive systems. Based on the recent advances in genetic engineering, we anticipate that antiviral transgenic Ae. aegypti exhibiting gene drive will soon emerge; however, close monitoring in simulated field conditions will be required to demonstrate the efficacy and utility of such transgenic mosquitoes.
The gene drive dilemma: We can alter entire species but should we?
6302J. Kahn, New York Times Magazine, 2020-01-08 20:03:00.
One early summer evening in 2018, the biologist Anthony James drove from his office at the University of California, Irvine, to the headquarters of the Creative Artists Agency, a sleek glass-and-steel high-rise in Los Angeles. There, roughly 200 writers, directors and producers — many of them involved in the making of science-and-technology thrillers — were gathered for an event called Science Speed Dating, where James and other scientists would explain their work. The sessions were organized, James told me, “in hopes of getting the facts at least somewhat straight.”
DNA ‘edit’ that could wipe out grey invaders
6249Levy, A., Scottish Daily Mail, 2020-01-07 19:25:25.
It is the big, brash invasive species whose advance has left the native red squirrel clinging on for survival in areas where once it thrived. But the march of the grey squirrel could be halted by a 'gene drive', say researchers at the laboratory responsible for Dolly the sheep.
Scenario analysis on the use of rodenticides and sex-biasing gene drives for the removal of invasive house mice on islands
6221M. E. Serr, R. X. Valdez, K. S. Barnhill-Dilling, J. Godwin, T. Kuiken and M. Booker, Biological Invasions, 2020-01-06 21:34:59.
Since the 1960s conservation efforts have focused on recovering island biodiversity by eradicating invasive rodents. These eradication campaigns have led to considerable conservation gains, particularly for nesting seabirds. However, eradications are complex and lengthy endeavors and are even more challenging when humans are co-inhabitants of the targeted island. Furthermore, the method of eradication matters and recent proposals to consider genetic technologies for rodent eradication require specific scrutiny. One such technology is the potential use of a gene drive for biasing offspring sex ratios in invasive house mice, Mus musculus, that would spread and prevent the production of one sex, allowing die-off from lack of reproduction and natural attrition. Practitioners can gain insight into the potential for adoption of this technology from examining stakeholder engagement. This paper uses scenario analysis to address the eradication of rodents on inhabited and uninhabited islands, by specifically comparing the traditional approach of using rodenticides with sex-biasing gene drives. Concurrently the International Union for Conservation of Nature is assessing the risks and value of gene drives in general for conservation. Hence, we make the case that the ethical challenges with the use of gene drive sex-biasing techniques and the effectiveness of this tool will rely as much on its public acceptance and its democratic use as the actual science used to construct the technology.
Red squirrels to thrive again in Britain as new plan considered to eradicate grey breed
6246Hudson, W., Express, 2020-01-06 19:17:19.
RED SQUIRRELS could soon be thriving in Britain again as a new plan to put an end to destructive grey squirrels is being developed. The 150 year reign of the grey squirrel could come to a halt from DNA editing to ensure all future females are born infertile. Researchers at the Roslin Institute want to create gene-edited squirrels for eventual release into the wild. The genetics laboratory is renowned for its 1996 creation of Dolly the Sheep, the world’s first mammal cloned from an adult cell.
Scientists want to hack grey squirrels to death
6243Cutlack, C., Gizmodo, 2020-01-06 19:11:01.
Scottish scientists are planning to hack the DNA of the often-hated grey squirrel, in hope that selectively breeding a broken female strain could lead to their eventual eradication from the wild. It's the only way a map of Scotland is likely to turn red in the foreseeable future.
Scientists behind Dolly the sheep want to edit squirrel DNA to get rid of greys and protect reds UK
6240Bedoya, D., Inforsurhoy, 2020-01-06 19:05:21.
The scientists who cloned Dolly the sheep are now targeting grey squirrels in a bid to rid Britain of them altogether.
First they cloned Dolly the sheep. Now they’re targeting grey squirrels
6218Leake, J., The Times, 2020-01-05 21:25:05.
For 150 years they have wreaked havoc on Britain’s woods and wildlife, but the destructive reign of the grey squirrel could soon be over — ended by DNA editing to ensure that all future females are born infertile. Researchers at the Roslin Institute, the genetics laboratory renowned for its 1996 creation of Dolly the Sheep, the world’s first mammal cloned from an adult cell, want to create gene-edited squirrels for eventual release into the wild.
Dolly the sheep scientists hope DNA editing can wipe out grey squirrels
6215McLaughlin, M., The Scotsman, 2020-01-05 21:20:21.
They have been poisoned, shot at, and stumbled into traps laid by those who regard them as a ruinous blight on the country’s woodland and wildlife. But now, the grey squirrel is facing arguably its biggest threat yet, with plans to harness the cutting edge of genetic science to bring their destructive reign to an end.
Beyond Mendelian genetics: Anticipatory biomedical ethics and policy implications for the use of CRISPR together with gene drive in humans.
6227M. W. Nestor and R. L. Wilson, Journal of Bioethical Inquiry, 2020:1-12. 2020-01-03 21:43:18.
Clustered regularly interspaced short palindromic repeats (CRISPR) genome editing has already reinvented the direction of genetic and stem cell research. For more complex diseases it allows scientists to simultaneously create multiple genetic changes to a single cell. Technologies for correcting multiple mutations in an in vivo system are already in development. On the surface, the advent and use of gene editing technologies is a powerful tool to reduce human suffering by eradicating complex disease that has a genetic etiology. Gene drives are CRISPR mediated alterations to genes that allow them to be passed on to subsequent populations at rates that approach one hundred per cent transmission. Therefore, from an anticipatory biomedical ethics perspective, it is possible to conceive gene drive being used with CRISPR to permanently ameliorate aberrant genes from wild-type populations containing mutations. However, there are also a number of possible side effects that could develop as the result of combining gene editing and gene drive technologies in an effort to eradicate complex diseases. In this paper, we critically analyse the hypothesis that the combination of CRISPR and gene drive will have a deleterious effect on human populations from an ethical perspective by developing an anticipatory ethical analysis of the implications for the use of CRISPR together with gene drive in humans.
Gene drives : equity demands civility
6184N. Kofler, Nature, 565:25. 2020-01-03 19:10:06.
At the 14th Conference of the Parties of the United Nations Convention on Biological Diversity late last year, I witnessed the rapid deterioration of a crucial discussion. It was on the potential of synthetic biology in environmental conservation. What started as heckling turned into a yelling match of misinformation. Such disruptive behaviour robbed the global community of a rare opportunity to debate gene drives in a meaningful way. Sidelined young scientists, country delegates and others watched in disbelief.
Technology Factsheet: Gene Drives
7265J. Lunshof, C. Shachar, R. Edison, A. Jayanti, Belfer Center for Science and International Affairs, 2020-01-01 17:03:29.
Gene drives can be defined as genetic elements that pass from parents to unusually high numbers of their offspring due to biased inheritance (sometimes referred to as the possession of “selfish” genetic elements).1,2 There are different ways of achieving this biased inheritance needed for a drive, but the shared outcome is one where the offspring of a parent carrying a certain genetic variant has over a 50% likelihood of inheriting it. With regular inheritance, in the absence of a gene drive, each of the two alleles carried by a parent are equally likely to be inherited by offspring. By implementing modern gene editing technology, such as CRISPR, gene drives can be manufactured by humans to intentionally suppress a target population or spread a trait through a population. For example, gene drives could be used to target weeds, spreading a trait that would reverse their evolved resistance to non-toxic herbicides. Gene drives could also be used for human health purposes, in particular for the control of vector-borne diseases, such as malaria through populations of mosquitos. There are many outstanding governance questions with regards to the specific research, development, testing, and deployment of gene drives—including who should be taking ownership of drafting regulations and policy. At this stage, few countries currently have regulations that are defined specifically for gene drive, and in most countries the closest relevant regulations are those written for a broader swath of gene editing technologies. As there becomes more momentum around the potentially unique opportunities of gene drives though, it is important for U.S. legislators and policymakers to remain engaged in the technology’s technical, ethical, and practical progress and consider technology-specific governance.
A typology of community and stakeholder engagement based on documented examples in the field of novel vector control
6032C. E. Schairer, R. Taitingfong, O. S. Akbari and C. S. Bloss, PLoS Neglected Tropical Diseases, 13:e0007863. 2019-12-30 20:46:44.
Background Despite broad consensus on the importance of community and stakeholder engagement (CSE) for guiding the development, regulation, field testing, and deployment of emerging vector control technologies (such as genetically engineered insects), the types of activities pursued have varied widely, as have the outcomes. We looked to previous CSE efforts for clarity about appropriate methods and goals. Our analysis yielded a typology of CSE, and related vocabulary, that describes distinctions that funders, organizers, and scholars should make when proposing or evaluating CSE. Methods We compiled available formal documentation of CSE projects, starting with projects mentioned in interviews with 17 key informants. Major features of these examples, including the initiators, target groups, timing, goals, and methods were identified using qualitative coding. Based on these examples, subcategories were developed for a subset of features and applied to the identified cases of CSE in the documents. Co-occurrence of subcategorized features was examined for patterns. Results We identified 14 documented examples CSE projects, which were comprised of 28 distinct CSE activities. We found no clear patterns with respect to timing. However, we found that grouping examples according to whether initiators or targets could enact the immediate desired outcome could help to clarify relationships between goals, methods, and targets.
These are the 5 most dystopian technologies of 2020 and beyond
6188M. Sullivan, FastCompany, 2019-12-28 19:13:46.
Tech is always both good and bad. But we live in a time when everything gets weaponized—ideas, images, ancient texts, biases, and even people. And technology provides the tools to do it easier, faster, and with less resources.
Biomphalaria glabrata Granulin Increases Resistance to Schistosoma mansoni Infection in Several Biomphalaria Species and Induces the Production of Reactive Oxygen Species by Haemocytes
13835J. R. Hambrook, A. A. Gharamah, E. A. Pila, S. Hussein and P. C. Hanington, Genes, 11:12. 2019-12-28 15:36:48.
In this study, we demonstrate that in vivo addition of Biomphalaria glabrata pro-granulin (BgGRN) can reduce Schistosoma mansoni infection success in numerous Biomphalaria sp. when challenged with different S. mansoni strains. We also demonstrate that cleavage of BgGRN into individual granulin subunits by elastase results in the stimulation of haemocytes to produce reactive oxygen species.
Mathematical modeling of self-contained CRISPR gene drive reversal systems
6023M. G. Heffel and G. C. Finnigan, Scientific Reports, 9:20050. 2019-12-27 20:31:43.
There is a critical need for further research into methods to control biological populations. Numerous challenges to agriculture, ecological systems, and human health could be mitigated by the targeted reduction and management of key species (e.g. pests, parasites, and vectors for pathogens). The discovery and adaptation of the CRISPR/Cas editing platform co-opted from bacteria has provided a mechanism for a means to alter an entire population. A CRISPR-based gene drive system can allow for the forced propagation of a genetic element that bypasses Mendelian inheritance which can be used to bias sex determination, install exogenous information, or remove endogenous DNA within an entire species. Laboratory studies have demonstrated the potency by which gene drives can operate within insects and other organisms. However, continued research and eventual application face serious opposition regarding issues of policy, biosafety, effectiveness, and reversal. Previous mathematical work has suggested the use of modified gene drive designs that are limited in spread such as daisy chain or underdominance drives. However, no system has yet been proposed that allows for an inducible reversal mechanism without requiring the introduction of additional individuals. Here, we study gene drive effectiveness, fitness, and inducible drive systems that could respond to external stimuli expanding from a previous frequency-based population model. We find that programmed modification during gene drive propagation could serve as a potent safeguard to either slow or completely reverse drive systems and allow for a return to the original wild-type population.
CRISPR-based gene-drives: from eukaryotes to prokaryotes
5934Nizet, V., Bioengineering Community, 2019-12-21 17:49:35.
Active genetics technology greatly biases transmission of genetic traits, bypassing traditional constraints of Mendelian inheritance and spreading rapidly through wild populations (1). Molecularly defined gene drive constructs in Saccharomyces cerevisiae were copied at efficiencies exceeding 99% when mated to wild yeast (2). Using active genetics to bias inheritance of desired alleles in laboratory mice appears to enable rapid assembly of otherwise impractical genotypes involving multiple homozygous genes (3). In another example, vector mosquito Anopheles stephensi was engineered to carry Cas9, a gRNA and antimalarial gene cassette and might be introduced to block propagation of the malaria parasite Plasmodium falciparum (4).
Experimental population modification of the malaria vector mosquito, Anopheles stephensi
6182T. B. Pham, C. H. Phong, J. B. Bennett, K. Hwang, N. Jasinskiene, K. Parker, D. Stillinger, J. M. Marshall, R. Carballar-Lejarazú and A. A. James, PLOS Genetics, 15:e1008440. 2019-12-19 19:05:32.
The experimental introduction of manipulated genes into insect species has a long history in basic genetics. Recent advances in genome editing technologies have spurred considerable effort to exploit these methodologies to provide genetic solutions to some of the worst medical and agricultural problems caused by insects. Insect population suppression and population modification approaches have been proposed to control transmission of vector-borne diseases, including malaria. We used small cage trials to explore the efficacy of non-drive and gene-drive releases to deliver anti-malarial effector genes to a vector mosquito, Anopheles stephensi. We show that both approaches can work to introduce genes to high percentages, but as expected, the gene-drive approaches were more efficient in that they needed only a single release with a much lower number of released insects. The gene-drive females in our studies exhibited a significant load that resulted in some cage populations going to extinction. Furthermore, the accumulation of drive-resistant target genes prevented full introduction of the transgenes in those cages that did not go extinct. While none of the strains evaluated here are proposed for open release, these laboratory cage trials reveal features that can be used to improve next-generation gene-drive strains for population modification.
Gene drives for schistosomiasis transmission control
6341T. Maier, N. J. Wheeler, E. K. O. Namigai, J. Tycko, R. E. Grewelle, Y. Woldeamanuel, K. Klohe, J. Perez-Saez, S. H. Sokolow, G. A. De Leo, T. P. Yoshino, M. Zamanian and J. Reinhard-Rupp, PLoS Neglected Tropical Diseases, 13:e0007833. 2019-12-19 18:18:55.
Schistosomiasis is one of the most important and widespread neglected tropical diseases (NTD), with over 200 million people infected in more than 70 countries; the disease has nearly 800 million people at risk in endemic areas. Although mass drug administration is a cost-effective approach to reduce occurrence, extent, and severity of the disease, it does not provide protection to subsequent reinfection. Interventions that target the parasites' intermediate snail hosts are a crucial part of the integrated strategy required to move toward disease elimination. The recent revolution in gene drive technology naturally leads to questions about whether gene drives could be used to efficiently spread schistosome resistance traits in a population of snails and whether gene drives have the potential to contribute to reduced disease transmission in the long run. Responsible implementation of gene drives will require solutions to complex challenges spanning multiple disciplines, from biology to policy. This Review Article presents collected perspectives from practitioners of global health, genome engineering, epidemiology, and snail/schistosome biology and outlines strategies for responsible gene drive technology development, impact measurements of gene drives for schistosomiasis control, and gene drive governance. Success in this arena is a function of many factors, including gene-editing specificity and efficiency, the level of resistance conferred by the gene drive, how fast gene drives may spread in a metapopulation over a complex landscape, ecological sustainability, social equity, and, ultimately, the reduction of infection prevalence in humans. With combined efforts from across the broad global health community, gene drives for schistosomiasis control could fortify our defenses against this devastating disease in the future.
Gene drive: progress and prospects
5795Wedell, N., T. A. R. Price and A. K. Lindholm, Proceedings of the Royal Society B: Biological Sciences, 286:20192709. 2019-12-19 14:25:02.
Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading nontarget species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release.
Transcontinental dispersal of Anopheles gambiae occurred from West African origin via serial founder events
14311H. Schmidt, Y. Lee, T. C. Collier, M. J. Hanemaaijer, O. D. Kirstein, A. Ouledi, M. Muleba, D. E. Norris, M. Slatkin, A. J. Cornel and G. C. Lanzaro, Communications Biology, 2. 2019-12-19 12:47:18.
Here we present population genomic analyses of 111 specimens sampled from west to east Africa, including the first whole genome sequences from oceanic islands, the Comoros.
The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes
5648Alcalay, Y., S. Fuchs, R. Galizi, F. Bernardini, R. E. Haghighat-Khah, D. B. Rusch, J. R. Adrion, M. W. Hahn, P. Tortosa and P. A. Papathanos, bioRxiv, 2019:860551. 2019-12-17 17:51:02.
Synthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X chromosome shredding operates through the targeted elimination of X-chromosome-bearing gametes during male spermatogenesis, resulting in males that have a high fraction of male offspring. Strains harboring autosomal constructs containing a modified endonuclease I-PpoI have now been developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion towards males. Data are being gathered for these strains for submission of regulatory dossiers for contained use and subsequent field release in West Africa. Since autosomal X shredders are transmitted in a Mendelian fashion and can be selected against their frequency in the population is expected to decline once releases are halted. However, any unintended transfer of the X-shredder to the Y-chromosome could theoretically change these dynamics: This could lead to 100% transmission of the newly Y-linked X-shredder to the predominant male-biased offspring and its insulation from negative selection in females, resulting in its potential spread in the population and ultimately to suppression. Here, we analyze plausible mechanisms whereby an autosomal X-shredder could become linked to the Y-chromosome after release and provide data regarding its potential for activity should it become linked to the Y-chromosome. Our results strongly suggest that Y-chromosome linkage through remobilization of the transposon used for the initial genetic transformation is unlikely, and that, in the unexpected event that the X-shredder becomes linked to the Y-chromosome, expression and activity of the X-shredder would likely be inhibited by meiotic sex chromosome inactivation. We conclude that a functioning X-shredding based Y-drive resulting from a naturally induced transposition or translocation of the transgene onto the Y-chromosome is unlikely.
Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O’nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strain
5634Mumford, J. D., C. A. Long, S. C. Weaver, K. Miura, E. Wang, R. Rotenberry, E. M. Dotson and M. Q. Benedict, " Journal of Medical Entomology, 56:936-941. 2019-12-17 16:55:10.
ransgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit known pathogens could be greater than the unmodified form. In this study, the ability to develop two human pathogens in these transgenic mosquitoes carrying a homing endonuclease which is expressed in the testes was compared with its nontransgenic siblings. Infections were performed with Plasmodium falciparum (Welch) and o’nyong-nyong virus (ONNV) and the results between the transgenic and nontransgenic sibling females were compared. There was no difference observed with ONNV isolate SG650 in intrathoracic infections or the 50% oral infectious dose measured at 14 d postinfection or in mean body titers. Some significant differences were observed for leg titers at the medium and highest doses for those individuals in which virus titer could be detected. No consistent difference was observed between the transgenic and nontransgenic comparator females in their ability to develop P. falciparum NF54 strain parasites. This particular transgene caused no significant effect in the ability of mosquitoes to become infected by these two pathogens in this genetic background. These results are discussed in the context of risk to human health if these transgenic individuals were present in the environment.
Genetically engineering wild mice to combat Lyme disease: An ecological perspective
5631Snow, A. A., BioScience, 69:746-756. 2019-12-17 16:51:55.
Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens’ hosts. For example, CRISPR- based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). Toward this goal, academic researchers are developing Lyme-resistant and tick-resistant white-footed mice, which are a primary pathogen reservoir for Lyme disease in the United States. If field trials on small, experimental islands are successful, the project would scale up to the larger islands of Nantucket and Martha’s Vineyard, Massachusetts, and possibly to the mainland, most likely with a local gene drive to speed the traits’ proliferation, pending approvals from relevant constituents. Despite considerable publicity, this project has yet to be evaluated by independent professional ecologists. In the present article, I discuss key ecological and evolutionary questions that should be considered before such genetically engineered mice are released into natural habitats
Design and analysis of CRISPR-based underdominance toxin-antidote gene drives
5626Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer, bioRxiv, 861435:861435. 2019-12-17 16:38:34.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based underdominance gene drive constructs employing toxin-antidote principles. These drives disrupt the wild-type version of an essential gene using a CRISPR nuclease (the toxin) while simultaneously carrying a recoded version of the gene (the antidote). Drives of this nature allow for releases that could be potentially confined to a desired geographic location. This is because such drives have a nonzero invasion threshold frequency, referring to the critical frequency required for the drive to spread through the population. We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters that have ubiquitous somatic expression. We also study several possible drive architectures, considering both “same-site” and “distant-site” systems, as well as several reciprocally targeting drives. Together, these drive variants provide a wide range of invasion threshold frequencies and options for both population modification and suppression. Our results suggest that CRISPR toxin-antidote underdominance drive systems could allow for the design of highly flexible and potentially confinable gene drive strategies.
Disrupting female flight in the vector Aedes aegypti
5624O'Leary, S. and Z. N. Adelman, bioRxiv, 862300:862300. 2019-12-17 16:35:43.
Aedes aegypti is a vector of dengue, chikungunya, and Zika viruses. Current vector control strategies such as community engagement, source reduction, and insecticides have not been sufficient to prevent viral outbreaks. Thus, interest in novel strategies involving genetic engineering is growing. Female mosquitoes rely on flight to mate with males and obtain a bloodmeal from a host. We hypothesized that knockout of genes specifically expressed in female mosquitoes associated with the indirect flight muscles would result in a flightless female mosquito. With the CRISPR-Cas9 system, we performed embryonic microinjections of Cas9 protein and guide RNAs specific to genes hypothesized to control flight in mosquitoes, and have obtained genetic knockouts in several genes specifically expressed in the flight-muscle, including those specific to female flight muscle. Analysis of the phenotype of these female-specific gene knockout mutants resulted in flightless females and flying males. While further assessment is required, this work lays the groundwork for a mechanism of population control that is female-specific for the Ae. aegypti vector.
The analytical review on futuristic use of CRISPR-Cpf1 aided gene drive technology
5618Satyam, R., N. Singh and T. Bhardwaj, International Journal of Trend in Scientific Research and Development, 2:525-530. 2019-12-17 16:27:59.
Organisms edited by gene editing or traditional selective breeding are typically less able to survive and reproduce which effectively prevents those alterations from spreading in the wild populations. This paper focuses on how the CRISPR-Cpf1 system can be used to build a Gene Drive capable of spreading particular alterations in the wild population, and its potential applications. Named for the ability to "drive" themselves and nearby genes through populations of organisms over many generations. Normally, the sexually reproducing organism comprises of 50-50% genetic information from both parents. But with gene drive, you can have 100% chance of passing a particular gene. The discovery of new Gene Editing Technology, based on the bacterial immune system, allow us to edit genome at specific sites with more precision, accuracy and ease. CRISPR Gene Drives including the edited version of the targeted gene and additional sequences with the DNA cutting Cpf1 protein and Guide RNA gene. When an organism containing a Gene Drive, mates with the wild counterparts, the offspring inherit one altered and one original copy of the target gene. The Guide RNAs Cpf1 directs to cut the original copy which is repaired by copying the altered gene as template synthesizing Gene Drive sequence in its place. Because the organism now has two identical copies of the alteration and the Gene Drive one on each chromosome, all of the organism will inherit both components. The same process will be repeated in subsequent generation causing the altered gene and Gene Drive to spread into the entire wild population. The Gene Drive technology has the potential to save millions of lives and give us unprecedented control over the natural world. This technology can be used to eradicate insect-born diseases, empower sustainable agriculture and promote ecological conservation.
Invasive insects: Management methods explored
5612McLaughlin, G. M. and P. K. Dearden, Journal of Insect Science, 19:1-9. 2019-12-17 16:18:09.
Invasive insect species can act as a plague across the globe, capable of vast expansion and rapid, proliferate reproduction. The spread of pathogens of serious diseases such as malaria and Zika virus and damages to agricultural crops number some of the afflictions invasive insects provide to humans alone. Additionally, an escape from predators can fail to keep invasive insects in check, providing potential threats such as extra resource competition to native species when insects invade. A variety of methods are employed to combat these invasive species, each with their own varying levels of success. Here, we explore the more traditional methods of invasive insect pest control, such as pesticides and biological control. In lieu of several unintended consequences resulting from such practices, we suggest some should be abandoned. We evaluate the potential of new techniques, in particular, those with a genetic component, regarding the costs, benefits and possible consequences of implementing them. And finally, we consider which techniques should be the focus of future research, if we truly wish to manage or even eradicate invasive insects in their introduced lands.
Winning the tug-of-war between effector gene design and pathogen evolution in vector population replacement strategies
5609Marshall, J. M., R. R. Raban, N. P. Kandul, J. R. Edula, T. M. León and O. S. Akbari, Frontiers in Genetics, 10:1072. 2019-12-17 16:13:33.
While efforts to control malaria with available tools have stagnated, and arbovirus outbreaks persist around the globe, the advent of clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing has provided exciting new opportunities for genetics-based strategies to control these diseases. In one such strategy, called “population replacement”, mosquitoes, and other disease vectors are engineered with effector genes that render them unable to transmit pathogens. These effector genes can be linked to “gene drive” systems that can bias inheritance in their favor, providing novel opportunities to replace disease-susceptible vector populations with disease-refractory ones over the course of several generations. While promising for the control of vector-borne diseases on a wide scale, this sets up an evolutionary tug-of-war between the introduced effector genes and the pathogen. Here, we review the disease-refractory genes designed to date to target Plasmodium falciparum malaria transmitted by Anopheles gambiae, and arboviruses transmitted by Aedes aegypti, including dengue serotypes 2 and 3, chikungunya, and Zika viruses. We discuss resistance concerns for these effector genes, and genetic approaches to prevent parasite and viral escape variants. One general approach is to increase the evolutionary hurdle required for the pathogen to evolve resistance by attacking it at multiple sites in its genome and/or multiple stages of development. Another is to reduce the size of the pathogen population by other means, such as with vector control and antimalarial drugs. We discuss lessons learned from the evolution of resistance to antimalarial and antiviral drugs and implications for the management of resistance after its emergence. Finally, we discuss the target product profile for population replacement strategies for vector-borne disease control. This differs between early phase field trials and wide-scale disease control. In the latter case, the demands on effector gene efficacy are great; however, with new possibilities ushered in by CRISPR-based gene editing, and when combined with surveillance, monitoring, and rapid management of pathogen resistance, the odds are increasingly favoring effector genes in the upcoming evolutionary tug-of-war.
Identification and characterisation of a Masculinizer homolog in the diamondback moth Plutella xylostella
5607Harvey-Samuel, T., V. C. Norman, R. Carter, E. Lovett and L. Alphey, Insect Molecular Biology, 2019:2019. 2019-12-17 16:09:12.
Recently, a novel sex-determination system was identified in the silkworm (Bombyx mori) in which a piRNA encoded on the female-specific W chromosome silences a Z-linked gene (Masculinizer) which would otherwise initiate male sex-determination and dosage compensation. Masculinizer provides various opportunities for developing improved genetic pest management tools. A pest lepidopteran in which a genetic pest management system has been developed, but which would benefit greatly from such improved designs, is the diamondback moth, Plutella xylostella. However, Masculinizer has not yet been identified in this species. Here, focusing on the previously described ?masculinizing? domain of B. mori Masculinizer, we identify P. xylostella Masculinizer (PxyMasc). We show that PxyMasc is Z-linked, regulates sex-specific alternative splicing of doublesex and is necessary for male survival. Similar results in B. mori suggest this survival effect is possibly through failure to initiate male dosage compensation. The highly conserved function and location of this gene between these two distantly related lepidopterans suggests a deep role for Masculinizer in the sex-determination systems of the Lepidoptera.
A novel drug-inducible sex separation technique for insects
5605Kandul, N. P., J. Liu, A. D. Hsu, B. A. Hay and O. S. Akbari, bioRxiv, 2019:2019.12.13.875716. 2019-12-17 16:05:02.
Large sterile male releases are the gold standard for most insect population control methods and thus precise sex sorting is essential to the success of these technologies. Sex sorting is especially important for mosquito control because female mosquitoes bite and transmit diseases. However, current methods for insect sex sorting have deficiencies as they are error prone, low throughput, expensive, reduce male fitness, or lack cross species adaptability. Here we describe a novel drug-inducible system for insect sex-separation that demonstrates proof-of-principle for positive sex selection in D. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin and rescues only one sex. Sex specific rescue is achieved by inserting the sex-specific introns, TraF and DsxM, into the coding sequence of antibiotic resistance genes, NeoR or PuroR. We engineer a dual sex-sorter gene cassette and demonstrate sex specific, constitutive expression of NeoR and PuroR proteins in females and males, respectively. When raised on geneticin supplements, this sex-sorter line established 100% positive selection for female progeny, while the food supplemented with puromycin generated 100% male progeny. This system is 100% efficient and operates at remarkably low fitness costs in D. melanogaster. Since the described system exploits a conserved sex-specific splicing mechanism and reagents, which are active in many insects, it has the potential to be adaptable to insect species of medical and agricultural importance.
Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elements
5602Oberhofer, G., T. Ivy and B. A. Hay, bioRxiv, 2019:2019.2012.2013.876169. 2019-12-17 16:01:29.
Gene drive-based strategies for modifying populations face the problem that genes encoding cargo and the drive mechanism are subject to separation, mutational inactivation, and loss of efficacy. Resilience, an ability to respond to these eventualities in ways that restore population modification with functional genes is needed for long-term success. Here we show that resilience can be achieved through cycles of population modification with Cleave and Rescue (ClvR) selfish genetic elements. ClvR comprises a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage. ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. Cycles of modification can in principal be carried out if two ClvR elements targeting different essential genes are located at the same genomic position, and one of them, ClvRn+1, carries a Rescue transgene from an earlier element, ClvRn. ClvRn+1 should spread within a population of ClvRn, while also bringing about a decrease in its frequency. To test this hypothesis we first show that multiple ClvRs, each targeting a different essential gene, function when located at a common chromosomal position in Drosophila. We then show that when several of these also carry the Rescue from a different ClvR, they spread to transgene fixation in populations fixed for the latter, and at its expense. Therefore, genetic modifications of populations can be overwritten with new content, providing an ongoing point of control.
A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus
5595Valderrama, J. A., S. S. Kulkarni, V. Nizet and E. Bier, Nature Communications, 10:5726. 2019-12-17 15:48:28.
Gene-drive systems in diploid organisms bias the inheritance of one allele over another. CRISPR-based gene-drive expresses a guide RNA (gRNA) into the genome at the site where the gRNA directs Cas9-mediated cleavage. In the presence of Cas9, the gRNA cassette and any linked cargo sequences are copied via homology-directed repair (HDR) onto the homologous chromosome. Here, we develop an analogous CRISPR-based gene-drive system for the bacterium Escherichia coli that efficiently copies a gRNA cassette and adjacent cargo flanked with sequences homologous to the targeted gRNA/Cas9 cleavage site. This “pro-active” genetic system (Pro-AG) functionally inactivates an antibiotic resistance marker on a high copy number plasmid with ~ 100-fold greater efficiency than control CRISPR-based methods, suggesting an amplifying positive feedback loop due to increasing gRNA dosage. Pro-AG can likewise effectively edit large plasmids or single-copy genomic targets or introduce functional genes, foreshadowing potential applications to biotechnology or biomedicine.
Development of genetic control strategies for insect pests using CRISPR/Cas9 Développement de méthodes de lutte génétique contre de l’insecte nuisible basé sur le system CRISPR/Cas9
18505E. Green, Université de Strasbourg, 2019-12-17 14:20:21.
nsect pest control remains an important economic, environmental, and public health challenge. CRISPR/Cas9 gene drive (GD) is a novel genetic control strategy. GDs are genetic systems that can rapidly invade a population. This manuscript presents my efforts to develop gene drives in two important pest species, Anopheles gambiae, a major vector of malaria, and Drosophila suzukii, a global crop pest. The goals of this project were to develop a suppression gene drive in D. suzukii, to reduce population size, and a modification drive in An. gambiae, to reduce malaria transmission. While I was unable to produce a functional gene drive in D. suzukii, the efforts and protocols presented here can serve as a baseline for future work in this economically important crop pest. In An. gambiae, I successfully characterized two transgenic lines, one of which significantly blocks malaria transmission to a rodent model. Finally, I present my efforts to engineer a new modification gene drive strategy, indirect gene drive.
Gene drives in Africa – A Podcast
5592Wakeford, T., etc Group, 2019-12-16 19:57:27.
In Episode #1 ETC's Tom Wakeford speaks with Ugandan lawyer and advocate Barbara Ntambirweki about gene drives, a powerful new genetic technology that can change species in the wild and make species go extinct.
New CRISPR system efficiently battles antibiotic resistance
5673Black, Samantha, The Science Advisory Board, 2019-12-16 19:02:07.
Researchers from the University of California San Diego have developed a brand new CRISPR-based gene-drive system that dramatically increases the efficiency of inactivation of genes responsible for antibiotic resistance. The new system is detailed on December 16 in Nature Communications. Genes conferring antibiotic resistance are often found on plasmids, circular forms of DNA that can replicate independently of the bacterial genome. Amplification effects of these plasmids can lead to the transfer of antibiotic resistance among bacteria. This poses a significant challenge to disrupt this function. Researchers have developed several cut-and-destroy methods but have had only moderate success with them.
Genetic Control of Mosquitoes
5588Alphey, L., Annual Review of Entomology, 59:205-224. 2019-12-16 19:01:55.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
Antibiotic resistance hoops countered by gene drive feedback loops
5670GEN, Genetic Engineering & Biotechnology News, 2019-12-16 18:56:57.
Where a gene drive that cuts and destroys plasmids may fail, a gene drive that cuts, pastes, and copies plasmids may succeed. The “where,” in this case, is an antibiotic-resistant bacterium that carries multiple copies of an antibiotic-resistance gene. That is, the target gene occurs on multiple copies of an “amplified” plasmid. If some plasmids remain intact, the antibiotic-resistance gene persists and may even be passed to other bacteria. To overcome this problem, scientists based at the University of California (UC), San Diego, developed a gene drive that incorporates a self-amplifying mechanism. Called Pro-AG, for “proactive” active genetics, it increases its efficiency through a positive feedback loop.
Tackling antibiotic resistance head-on with CRISPR
5937Thomas, L., News Medical Life Sciences, 2019-12-16 17:58:59.
With modern advances in genetic engineering occurring almost every day, the latest discovery concerns antibiotic resistance. Using the powerful gene editor CRISPR, scientists reported the development of a gene-drive system that is 100 times as efficient as other current systems at inactivating a specific bacterial gene responsible for making the bacterium antibiotic-resistant and which is present as multiple copies within the same bacterial cell. The paper, published on December 16, 2019, in the journal Nature Communications, uses the technology called active genetics, pioneered by biologists at UC San Diego.
The bold plan to end malaria with a gene drive
5462VOX, 2019-12-13 16:52:47.
How genetically engineered mosquitoes might defeat a disease that kills millions of children. This describes gene drive and features work from a group (Target Malaria) that is developing this technology for use against malaria
Gene Drives: Assessing the benefits & risks
5684Creighton, J., Future of Life, 2019-12-05 19:20:26.
Most people seem to understand that malaria is a pressing problem, one that continues to menace a number of areas around the world. However, most would likely be shocked to learn the true scale of the tragedy. To illustrate this point, in 2017, more than 200 million people were diagnosed with malaria. By the year’s close, nearly half a million people had died of the disease. And these are the statistics for just one year. Over the course of the 20th century, researchers estimate that malaria claimed somewhere between 150 million and 300 million lives. With even the lowest figure, the death toll is still more than World War I, World War II, the Vietnam War, and the Korean War combined. Although its pace has slowed in recent years, according to the World Health Organization, malaria remains one of the leading causes of death in children under five. However, there is new hope, and it comes in the form of CRISPR gene drives.
An Initial Framework for the Environmental Risk Assessment of Synthetic Biology-Derived Organisms with a Focus on Gene Drives.
16281W. G. Landis, E. A. Brown and S. Eikenbary, Synthetic Biology 2020: Frontiers in Risk Analysis and Governance. Risk, Systems and Decisions., 2019-11-29 17:16:37.
We apply the structure of source-stressor-habitat-effect-impact pathway derived from the relative risk model (Landis and Wiegers 2005) and as was demonstrated to be applicable in the National Academy of Sciences, Engineering and Medicine (NASEM) 2016 report Gene Drives on the Horizon. This relative risk model is now calculated employing Bayesian networks and has been applied to forestry management (Ayre and Landis 2012), infectious disease (Ayre et al. 2014), invasive species (Herring et al. 2015), contaminated sites (Landis et al. 2017a; Johns et al. 2017), and watershed management (Hines and Landis 2014; Graham et al. 2019).
Wiping out the daughters: Burkina Faso’s controversial mosquito experiment
5679Boersma, H. and J. Bastmeijer, The Guardian, 2019-11-18 19:10:31.
A radical experiment to genetically modify a strain of mosquito in order to stop them breeding malaria-carrying daughters is one of the latest efforts to tackle the deadly scourge of malaria
Rodent gene drives for conservation: opportunities and data needs
6386J. Godwin, M. Serr, K. Barnhill-Dilling, D. V. Blondel, P. R. Brown, K. Campbell, J. Delborne, A. L. Lloyd, K. P. Oh, T. A. A. Prowse, R. Saah and P. Thomas, Proceedings of the Royal Society B-Biological Sciences, 286:20191606. 2019-11-10 16:22:06.
Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge gaps remain in a number of areas. This paper is focused on what is currently known about natural and developing synthetic gene drive systems in mice, some key areas where key knowledge gaps exist, findings in a variety of disciplines relevant to those gaps and a brief consideration of how engagement at the regulatory, stakeholder and community levels can accompany and contribute to this effort. Our primary species focus is the house mouse, Mus musculus, as a genetic model system that is also an important invasive pest. Our primary application focus is the development of gene drive systems intended to reduce reproduction and potentially eliminate invasive rodents from islands. Gene drive technologies in rodents have the potential to produce significant benefits for biodiversity conservation, human health and food security. A broad-based, multidisciplinary approach is necessary to assess this potential in a transparent, effective and responsible manner.
The impact of local population genetic background on the spread of the selfish element Medea-1 in red flour beetles
6379S. A. Cash, M. A. Robert, M. D. Lorenzen and F. Gould, Ecology and Evolution, 12:1-12. 2019-11-10 16:06:41.
Selfish genetic elements have been found in the genomes of many species, yet our understanding of their evolutionary dynamics is only partially understood. A number of distinct selfish Medea elements are naturally present in many populations of the red flour beetle (Tribolium castaneum). Although these Medea elements are predicted by models to increase in frequency within populations because any offspring of a Medea-bearing mother that do not inherit at least one Medea allele will die, experiments demonstrating an increase in a naturally occurring Medea element are lacking. Our survey of the specific Medea element, M-1, in the United States showed that it had a patchy geographic distribution. From the survey, it could not be determined if this distribution was caused by a slow process of M-1 colonization of discrete populations or if some populations lacked M-1 because they had genetic factors conferring resistance to the Medea mechanism. We show that populations with naturally low to intermediate M-1 frequencies likely represent transient states during the process of Medea spread. Furthermore, we find no evidence that genetic factors are excluding M-1 from US populations where the element is not presently found. We also show how a known suppressor of Medea can impair the increase of M-1 in populations and discuss the implications of our findings for pest-management applications of Medea elements.
Gene Drive and Thinking Animals
5541Island Conservation, 2019-11-04 20:54:55.
Royden Saah, Island Conservation's GBIRd program manager, recently spoke at the Thinking Animals Summit alongside Leilani Münter, a former professional race car driver and environmental activist. The Genetic Biocontrol of Invasive Rodents partnership (GBIRd) is designed for exactly that purpose. The partnership is made up of governments, NGOs, and research universities that are dedicated to understanding if the use of gene drives in mice can effectively eradicate invasive rodents on islands as well as the social implications of this science.
Gene Drives and new genetic manipulation in agriculture
5995Terra de Direitos, 2019-10-23 15:43:54.
Gene drives are forms of genetic editing or manipulation of live organisms. They are the most dangerous forms of transgenics which edit genetic characteristics without necessarily including a new gene, but rather manipulating existing genes of live organisms, i.e. live organism genetic information microsurgery. The technique uses enzymes which “cut and paste” (such as CrisPR/Cas9) genes of organisms that reproduce sexually – such as plants like maize and mosquitoes – without necessarily introducing genes from other organisms or synthetic genes. Produced by the National Agroecology Articulation (ANA) Biodiversity Working Group, a body that congregates different social organizations and movements, the video seeks to explain in an educational way how this new biotechnology is looming as a threat to the environment, agricultural biodiversity and society.
A Controversial Swarm Of Genetically Modified Mosquitoes In A Lab In Italy
5527NPR, 2019-10-20 19:41:57.
An international team of scientists is conducting a controversial experiment in Italy. The experiment is designed to test genetically modified mosquitoes that researchers hope could provide a powerful new weapon to fight malaria, which remains one of the world's greatest scourges.
Evolutionary simulations of Z-linked suppression gene drives
6643L. Holman, Proceedings of the Royal Society B-Biological Sciences, 286:1-9. 2019-10-09 20:23:58.
Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z-linked gene drives to control species with ZW sex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals include Z-linked 'W-shredders', which would suppress populations by cleaving the W chromosome and causing females to produce only sons, as well as Z-linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposed Z-linked gene drives, and to produce recommendations regarding their design and use. The simulations show that W-shredders are likely to be highly effective at eradicating populations provided that resistance to W-shredding cannot evolve. However, W-shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.
‘We don’t want to be guinea pigs’: how one African community is fighting genetically modified mosquitoes
15233A. Pujol-Mazzini, The Telegraph, 2019-10-08 16:47:08.
Researchers from the Target Malaria consortium, a not-for-profit research group funded by the Bill & Melinda Gates Foundation and various research institutions, have developed a mosquito in their laboratory that can kill off its own species by spreading a faulty gene. If it works in the wild, the technology – called gene drive – could help eliminate malaria where decades of efforts involving bed nets, repellents and insecticides have failed.
Threshold-Dependent Gene Drives in Wild Populations – A Podcast
6900G. A. Backus and J. A. Delborne, BioScience Talks, 2019-10-08 14:04:47.
By altering the heritability of certain traits, gene drive technologies have the potential to spread desired genes through wild populations. In practice, this could lead to mosquito populations that, for example, bear traits making them resistant to the spread of malaria. Despite the huge potential for improving human well-being, concern exists that gene drives could fail in the wild or spread beyond their intended target populations. Writing in BioScience, Dr. Greg Backus, a postdoctoral researcher at the University of California, Davis, and Jason Delborne, Associate Professor of Science Policy and Society at North Carolina State University's Genetic Engineering and Society Center, describe a potential solution. Threshold-dependent gene drives could limit the spread of wild-released gene drives to target populations, increasing control and reducing the risk of unchecked spread. The authors joined us on this episode of BioScience Talks to discuss the potential of these gene drives—and also some of the questions of controllability, spread, and ecological uncertainty that relate to them. Read the article. Listen to our previous podcast on gene drives.
Efforts to enhance safety measures for CRISPR/Cas-based gene drive technology in Japan
6035T. Tanaka, N. Tanaka, Y. Nagano, H. Kanuka, D. S. Yamamoto, N. Yamamoto, E. Nanba and T. Nishiuch, Journal of Environment and Safety, 2019-10-07 20:47:13.
Gene drive is a powerful system that can spread a desirable genetic trait into an entire species and/or population of a certain region, bypassing Mendelian rules of inheritance. Recently, one of the genome editing technologies, CRISPR/Cas, has been developed, making it easier to use gene drive in many different organisms. However, gene drive has potential risks that impact genetic diversity when organisms produced by CRISPR/Cas-based Gene Drive Technology (CCGDT) are accidentally released; therefore, a high degree of prudence is required when CCGDT is used. In Japan, a Working Group on Gene Drive has been established in the Academic Association for Promotion of Genetic Studies (AAPGS), and a Statement on the Handling of Gene Drive was issued to the public including research institute across Japan, after comprehensive and extensive discussions by the working group in order to reduce risks posed by CCGDT. A national-wide survey on CCGDT was implemented. The survey revealed that those in managerial positions including members and secretariats of institutional review boards on recombinant DNA, and biosafety officers are conscious of CCGDT, and efforts to grasp experimental plans involving CCGDT are made by utilizing an application form for recombinant DNA experiment. In contrast, potential risks of CCGDT are not understood by many researchers. All stakeholders need to disseminate potential risks and preventive measures regarding CCGDT to all researchers who may wish to use this technology. Researchers should use CCGDT upon understanding its potential risks and taking necessary measures. This report refers to how safety measures for CRISPR/Cas-based gene drive technology which has potential risks to ecological system has been discussed and results of national-wide questionnaire survey on gene drive in Japan based on the poster presentation at the Asian Conference on Safety & Education in Laboratory 2018.
Gene drives in Wisconsin agriculture: What are they, and should you support it?
6026Jones, M. and Mitchell, P. D., Renk Agribusiness Institute, 2019-10-02 20:34:10.
Spotted wing drosophila and citrus psyllid are not serious economic problems for Wisconsin agriculture. However, these and other smaller, geographically limited applications of gene drives are excellent ways to prove the concept and refine the methods. Pending the outcome of these limited-scale applications, we are likely to eventually see implications for row crop agriculture such as the management of serious and widespread pests such like corn rootworm, European corn borer, soybean aphid and Colorado potato beetle. Applications which could provide tremendous benefits to Wisconsin producers.
Gene Drive Mosquitoes: Ethics, Environment and Efficacy
18233L. Wilburn, ScienceInnovationUnion, 2019-09-20 17:06:38.
The Bill and Melinda Gates foundation has recently donated over $75 million to fund gene drive mosquito research by Target Malaria , a consortium that aims to develop technology for malaria control. The first planned release of gene drive mosquitoes is set to happen over the next two years in Burkina Faso, West Africa. But what exactly is gene drive, why do we need it and what are the wider implications of the technology? Malaria is a parasitic disease spread by the bite of the female Anopheles mosquito. Malaria can present as a range of symptoms including, mild fever, muscle pains (which can progress to severe malaria where the patient can experience severe anaemia and bleeding), renal failure, neurological disorders and death. In 2017, there were an estimated 219 million cases and 435,000 deaths attributed to malaria (1). Over 91% of these cases occurred in the Africa region, and children under the age of 5 were at the highest risk of contracting severe malaria. Fortunately, due to interventions such as insecticide-treated bed nets, indoor spraying of insecticides and improved medical infrastructure, from 2010-2017 malaria deaths were reduced by an estimated 28% (1). However, these control efforts may be severely jeopardised due to the rapid emergence of resistance to all insecticide classes and the most effective anti-malarial drugs (2, 3). Currently, there are only five classes of insecticides approved for public health use. In areas such as West Africa, there are multi-resistant mosquitoes which show resistance to all insecticide classes (4). Therefore, if the World Health Organisation (WHO) is to meet its goal of reducing global malaria by 90% by 2030, novel and effective strategies for malaria control must be identified (5). One such proposed strategy is gene drive mosquitoes.
Threshold-Dependent Gene Drives in the Wild: Spread, Controllability, and Ecological Uncertainty
6946G. A. Backus and J. A. Delborne, BioScience, 69:900-907. 2019-09-18 16:02:59.
Gene drive technology could allow the intentional spread of a desired gene throughout an entire wild population in relatively few generations. However, there are major concerns that gene drives could either fail to spread or spread without restraint beyond the targeted population. One potential solution is to use more localized threshold-dependent drives, which only spread when they are released in a population above a critical frequency. However, under certain conditions, small changes in gene drive fitness could lead to divergent outcomes in spreading behavior. In the face of ecological uncertainty, the inability to estimate gene drive fitness in a real-world context could prove problematic because gene drives designed to be localized could spread to fixation in neighboring populations if ecological conditions unexpectedly favor the gene drive. This perspective offers guidance to developers and managers because navigating gene drive spread and controllability could be risky without detailed knowledge of ecological contexts.
Scientists release sterile mosquitoes in Burkina to fight malaria
17024T. Ndiaga, Reuters, 2019-09-18 13:18:20.
Scientists in Burkina Faso have deployed a new weapon in the fight against malaria, and waded into a thorny bioethics debate, by letting loose thousands of genetically sterilized mosquitoes.Their experiment is the first outside the lab to release genetically altered mosquitoes in the hope of reducing their ability to spread the often deadly disease. It works using a technique called a gene drive, which edits and then propagates a gene in a population - in this case to prevent males from producing offspring. Investments in anti-malarial drugs, mosquito nets and insecticides have slowed malaria over the past two decades in Africa, which accounts for more than 90% of global cases. But malaria still killed more than 400,000 people across the continent in 2017, and the World Health Organization says progress against the disease is stalling, leading researchers to push for fresh approaches.
Gene Drive Technologies: Powerful and destructive
5510SWISSAID, 2019-09-16 19:05:21.
Gene drive organisms can put our environment, food and health in danger: this is made clear by the video from SWISSAID, the Alliance for GMO-free Switzerland and the ETC Group.
Malaria eradication within a generation: ambitious, achievable, and necessary
12533R. G. A. Feachem, I. Chen, O. Akbari, A. Bertozzi-Villa, S. Bhatt, F. Binka, M. F. Boni, C. Buckee, J. Dieleman, A. Dondorp, A. Eapen, N. Sekhri Feachem, S. Filler, P. Gething, R. Gosling, A. Haakenstad, K. Harvard, A. Hatefi, D. Jamison, K. E. Jones, C., Lancet, 394:1056-1112. 2019-09-13 15:21:30.
50 years after a noble but flawed attempt to eradicate malaria in the mid-20th century, the global malaria community is once again seriously considering eradication. Momentum towards eradication has been building for decades, and more than half of the world’s countries are now malaria free.
Genetically engineered mosquitoes out of control
4534GM Watch, GM Watch, 2019-09-11 00:00:00.
According to a new scientific publication, genetically engineered mosquitoes produced by the biotech company Oxitec (Intrexon) have escaped human control after trials in Brazil. They are now spreading in the environment. The yellow fever mosquitoes (Aedes aegypti) are genetically engineered to make it impossible for their offspring to survive. After release they were supposed to mate with female mosquitoes of the species which transmit infectious diseases, such as Dengue fever, to diminish the natural populations.
Dit Afrikaanse dorp krijgt, als eerste plek ter wereld, gentechmuggen tegen malaria
5676Boersma, Hidde, de Volkskrant, 2019-09-09 19:06:00.
Dit Afrikaanse dorp krijgt, als eerste plek ter wereld, gentechmuggen tegen malaria
A 2017 horizon scan of emerging issues for global conservation and biological diversity
4067Sutherland, WJB, P.; Broad, S.; Clout, M.; Connor, B.; Cote, I. M.; Dicks, L. V.; Doran, H.; Entwistle, A. C.; Fleishman, E.; Fox, M.; Gaston, K. J.; Gibbons, D. W.; Jiang, Z.; Keim, B.; Lickorish, F. A.; Markillie, P.; Monk, K. A.; Pearce-Higgins, J. W.; Peck, L. S.; Pretty, J.; Spalding, M. D.; Tonneijck, F. H.; Wintle, B. C.; Ockendon, N., Trends in Ecology & Evolution, 32:31-40. 2019-09-09 00:00:00.
We present the results of our eighth annual horizon scan of emerging issues likely to affect global biological diversity, the environment, and conservation efforts in the future. The potential effects of these novel issues might not yet be fully recognized or understood by the global conservation community, and the issues can be regarded as both opportunities and risks. A diverse international team with collective expertise in horizon scanning, science communication, and conservation research, practice, and policy reviewed 100 potential issues and identified 15 that qualified as emerging, with potential substantial global effects. These issues include new developments in energy storage and fuel production, sand extraction, potential solutions to combat coral bleaching and invasive marine species, and blockchain technology.
Herbicide resistant weeds: A call to integrate conventional agricultural practices, molecular biology knowledge and new technologies
6040V. E. Perotti, A. S. Larran, V. E. Palmieri, A. K. Martinatto and H. R. Permingeat, Plant Science, 290:110255. 2019-09-06 21:01:14.
Herbicide resistant (HR) weeds are of major concern in modern agriculture. This situation is exacerbated by the massive adoption of herbicide-based technologies along with the overuse of a few active ingredients to control weeds over vast areas year after year. Also, many other anthropological, biological, and environmental factors have defined a higher rate of herbicide resistance evolution in numerous weed species around the world. This review focuses on two central points: 1) how these factors have affected the resistance evolution process; and 2) which cultural practices and new approaches would help to achieve an effective integrated weed management. We claim that global climate change is an unnoticed factor that may be acting on the selection of HR weeds, especially those evolving into non-target-site resistance mechanisms. And we present several new tools –such as Gene Drive and RNAi technologies- that may be adopted to cope with herbicide resistance spread, as well as discuss their potential application at field level. This is the first review that integrates agronomic and molecular knowledge of herbicide resistance. It covers not only the genetic basis of the most relevant resistance mechanisms but also the strengths and weaknesses of traditional and forthcoming agricultural practices.
Gene Drives: Experience with gene drive systems that may inform an environmental risk assessment
4583Rüdelsheim, PKJS, G., COGEM, 2019-09-05 00:00:00.
Gene drives are genetic mechanisms that allow for a trait to be propagated throughout a population; beyond Mendelian inheritance. Active in sexually-reproducing species, they are powerful tools to “drive”; a gene, i.e. increase its frequency, independent of external selection pressure. They have been proposed; as offering solutions for many challenges in public health, agriculture, conservation and others. They have; inspired researchers to use gene drives to combat diseases transmitted by insects such as malaria,; dengue and Zika.; For decennia attempts have been made to use or modify naturally occurring gene drive mechanisms. Yet,; natural gene drives have their limitations. Transposable element-based drives turned out to be not efficient; enough. Moreover, they cannot be directed. Translocation drives are hard to establish and suffer from a; high fitness cost. Others are only active in specific species (e.g. meiotic drive, MEDEA).
Guidance for IBCs: Regulatory requirements for contained research with GMOs containing engineered gene drives
16086Office of the Gene Technology Regulator, Australian Government, Department of Health, 2019-09-01 15:35:42.
This document provides guidance for Institutional Biosafety Committees (IBCs) and researchers on the regulatory requirements for organisms containing engineered ‘gene drives’, including the physical containment (PC) level of facilities for notifiable low risk dealings (NLRDs). Gene drives are genetic elements that are favoured for inheritance, and which can therefore spread through populations at a greater rate than genes with standard Mendelian inheritance. Gene drives can only spread from sexually reproducing parents to their offspring. If gene technology is used to introduce or create a gene drive in an organism, the resulting organism will be a GMO and subject to regulation under the Gene Technology Act 2000.
Autonomy of Nations and Indigenous Peoples and the Environmental Release of Genetically Engineered Animals with Gene Drives
12398Z. Meghani, Global Policy, 10:554-568. 2019-08-05 18:30:26.
This article contends that the environmental release of genetically engineered (GE) animals with heritable traits that are patented will present a challenge to the efforts of nations and indigenous peoples to engage in self-determination. The environmental release of such animals has been proposed on the grounds that they could function as public health tools or as solutions to the problem of agricultural insect pests. This article brings into focus two political-economic-legal problems that would arise with the environmental release of such organisms. To address those challenges, it is proposed that nations considering the environmental release of GE animals must take into account the underlying circumstances and policy failures that motivate arguments for the use of the modified animals. Moreover, countries must recognize that the UN International Covenant on Civil and Political Rights and the UN International Covenant on Economic, Social and Cultural Rights place on them an obligation to ensure that GE animals with patented heritable traits are not released without the substantive consent of the nations or indigenous peoples that could be affected.
Transforming insect population control with precision guided sterile males with demonstration in flies
5905Kandul, N. P., J. Liu, H. M. Sanchez C, S. L. Wu, J. M. Marshall and O. S. Akbari, Nature Communications, 10:84. 2019-08-01 16:09:46.
The sterile insect technique (SIT) is an environmentally safe and proven technology to suppress wild populations. To further advance its utility, a novel CRISPR-based technology termed precision guided SIT (pgSIT) is described. PgSIT mechanistically relies on a dominant genetic technology that enables simultaneous sexing and sterilization, facilitating the release of eggs into the environment ensuring only sterile adult males emerge. Importantly, for field applications, the release of eggs will eliminate burdens of manually sexing and sterilizing males, thereby reducing overall effort and increasing scalability. Here, to demonstrate efficacy, we systematically engineer multiple pgSIT systems in Drosophila which consistently give rise to 100% sterile males. Importantly, we demonstrate that pgSIT-generated sterile males are fit and competitive. Using mathematical models, we predict pgSIT will induce substantially greater population suppression than can be achieved by currently-available self-limiting suppression technologies. Taken together, pgSIT offers to potentially transform our ability to control insect agricultural pests and disease vectors.
Viral gene drive in herpesviruses
5917Walter, M. and E. Verdin, bioRxiv, 2019:717017. 2019-07-30 16:38:14.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses.
Combinations of Spok genes create multiple meiotic drivers in Podospora
7240A. A. Vogan, S. L. Ament-Velásquez, A. Granger-Farbos, J. Svedberg, E. Bastiaans, A. J. M. Debets, V. Coustou, H. Yvanne, C. Clavé, S. J. Saupe and H. Johannesson, eLife, 8:e46454. 2019-07-26 15:53:58.
Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74–167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.
A family of killers
7238M. De Carvalho and S. E. Zanders, eLife, 8:e49211. 2019-07-26 15:50:06.
Spok genes are meiotic drivers that increase their own chances of transmission by killing gametes that do not inherit them.
Gene Drives in Africa: Civil Society Speaks Out
13132African Centre for Biodiversity, 2019-07-26 13:51:13.
On Monday 1st July 2019, Target Malaria announced the release of genetically modified (GM) sterile male mosquitoes in Bana, a village in Burkina Faso – the first GM insect to be released in Africa. This is Phase I – by Phase III, Target Malaria aims to release gene drive mosquitoes. This release occurred despite strong opposition from civil society, in Burkina Faso, and across the continent. In this video, key CSO figures discuss their concerns regarding gene drive technology and explain how their governments, and the Africa Union’s, position on gene drives, has been captured.
Assessment of a split homing based gene drive for efficient knockout of multiple genes
5915Kandul, N. P., J. Liu, A. Buchman, V. M. Gantz, E. Bier and O. S. Akbari, bioRxiv, 2019:706929. 2019-07-18 16:34:25.
Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host-encoded genes have been identified that are important for pathogen transmission, targeting these genes using guide RNAs as cargo genes linked to drives may provide a robust method to prevent transmission. However, effectiveness of the inclusion of additional guide RNAs that target separate host encoded genes has not been thoroughly explored. To test this approach, here we generated a split-HGD in Drosophila melanogaster that encoded a drive linked effector consisting of a second gRNA engineered to target a separate host encoded gene, which we term a gRNA-mediated effector (GME). This design enabled us to assess homing and knockout efficiencies of two target genes simultaneously, and also explore the timing and tissue specificity of Cas9 expression on cleavage/homing rates. We demonstrate that inclusion of a GME can result in high efficiency of disruption of its target gene during super-Mendelian propagation of split-HGD. However, maternal deposition and embryonic expression of Cas9 resulted in the generation of drive resistant alleles which can accumulate and limit the spread of such a drive. Alternative design principles are discussed that could mitigate the accumulation of resistance alleles while incorporating a GME.
The potential of genomics for restoring ecosystems and biodiversity
13616M. F. Breed, P. A. Harrison, C. Blyth, M. Byrne, V. Gaget, N. J. C. Gellie, S. V. C. Groom, R. Hodgson, J. G. Mills, T. A. A. Prowse, D. A. Steane and J. J. Mohr, Nature Reviews Genetics, 20:615-628. 2019-07-12 13:13:41.
Existing and emerging genomics tools offer the potential to improve the odds of achieving these targets. These tools include population genomics that can improve seed sourcing, meta-omics that can improve assessment and monitoring of restoration outcomes, and genome editing that can generate novel genotypes for restoring challenging environments.
Self-destructing mosquitoes and sterilized rodents: the promise of gene drives
6645M. Scudellari, Nature, 571:160-162. 2019-07-09 20:27:18.
Altering the genomes of entire animal populations could help to defeat disease and control pests, but researchers worry about the consequences of unleashing this new technology.
Synthetic Biology and the United Nations
7967H.-E. Lai, C. Canavan, L. Cameron, S. Moore, M. Danchenko, T. Kuiken, Z. Sekeyová and P. S. Freemont, Trends in Biotechnology, 37:1146-1151. 2019-06-27 14:42:54.
Synthetic biology is a rapidly emerging interdisciplinary field of science and engineering that aims to redesign living systems through reprogramming genetic information. The field has catalysed global debate among policymakers and publics. Here we describe how synthetic biology relates to these international deliberations, particularly the Convention on Biological Diversity (CBD).
Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment
13625V. L. Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz, bioRxiv, 684597. 2019-06-27 13:35:03.
CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise safety concerns for unintended gene propagation. Herein, we address this by splitting the two drive components, Cas9 and gRNAs, into separate alleles to form a novel trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes.
Biological control of pests and a social model of animal welfare
16284A. Mankad, U. Kennedy and L. Carter, Journal of Environmental Management, 247:313-322. 2019-06-25 17:21:12.
We consider the role of perceived humaneness or, more accurately, animal welfare as it relates to managing invasive species from a scientific and social perspective. In order to highlight and articulate particular nuances and standards across different pest control contexts, we use three case examples (feral cats, wild rabbits, and invasive cane toads) and explore where biological pest control and animal welfare interests intersect.
Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection on Islands: Workshop Report
11581M. Farooque, S. K. Barnhill-Dilling, J. Shapiro and J. Delborne, North Carolina State University, 2019-06-01 15:28:38.
The “Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection” workshop was held on the North Carolina State University campus in Raleigh, NC on March 7-8, 2019, aiming to convene a diverse group of stakeholders, scientists, funders, and leaders for an exploration of perspectives on the development of a gene drive mouse for restoring biodiversity on islands. Information collected at the workshop is presented in this report to inform upcoming decisions by the NCSU-Safe Genes research team about research, testing, and potential deployment of technologies (the Safe Genes program does not fund any environmental releases of gene drive modified organisms), as well as future engagement activities.
Vereinigung Deutscher Wissenschaftler e.V. | Gene Drive Symposium-Critical Science Switzerland
6674Critical Scientists Switzerland; European Network of Scientists for Social and Environmental Responsibility; Vereinigung Deutscher Wissenschaftler, 2019-05-24 18:26:07.
Gene Drives: A report on their science, applications, social aspects, ethics and regulations
6670H. Dressel, Critical Scientists Switzerland; European Network of Scientists for Social and Environmental Responsibility; Vereinigung Deutscher Wissenschaftler, 2019-05-17 18:00:50.
Engineered Gene Drives are a new form of genetic modification that provides the tools for permanently modifying or potentially even eradicating species or populations in the wild. Unlike the previous genetically modified organisms (GMOs), gene drive organisms (GDOs) are not meant to stay where they are released, but instead are designed and purpose-built to spread and to drive their modified genes far and wide into wild populations.
Gene drive organisms: What Africa should know about actors, motives and threats to biodiversity and food systems
5923Sirinathsinghji, E., African Centre for Biodiversity., 2019-05-13 16:51:45.
In this briefing paper, we set out the key issues that our governments should have addressed with African civil society before endorsing positions and setting the benchmark for Africa-wide policy. In this regard, we point out that, while the impetus for the AU position might well have been gene drive technologies proposed by the Gates-funded Target Malaria consortium, as a tool to reduce the transmission of malaria on the continent, the debate about gene drive organisms goes well beyond gene drive mosquitoes. Plans by gene drive developers target pests, pollinators, weeds and the speeding up of plant breeding programmes. The logic of using these technologies in agriculture relies on the continued deception that exceedingly complex problems in the food system in Africa can be resolved simply by new high-tech innovations, while downplaying their potential risks to biodiversity and livelihoods.
Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating
11202J. J. Bull, C. H. Remien and S. M. Krone, Evolution Medicine and Public Health, 2019:66-81. 2019-05-11 14:03:57.
Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology).
Improving plant-resistance to insect-pests and pathogens: The new opportunities through targeted genome editing
6176D. S. Bisht, V. Bhatia and R. Bhattacharya, Seminars in Cell & Developmental Biology, 96:65-76. 2019-05-08 18:53:44.
The advantages of high input agriculture are fading away due to degenerating soil health and adverse effects of climate change. Safeguarding crop yields in the changing environment and dynamics of pest and pathogens, has posed new challenges to global agriculture. Thus, integration of new technologies in crop improvement has been imperative for achieving the breeding objectives in faster ways. Recently, enormous potential of genome editing through engineered nucleases has been demonstrated in plants. Continuous refinements of the genome editing tools have increased depth and breadth of their applications. So far, genome editing has been demonstrated in more than fifty plant species. These include model species like Arabidopsis, as well as important crops like rice, wheat, maize etc. Particularly, CRISPR/Cas9 based two component genome editing system has been facile with wider applicability. Potential of genome editing has unfurled enormous possibilities for engineering diverse agronomic traits including durable resistance against insect-pests and pathogens. Novel propositions of developing insect and pathogen resistant crops by genome editing include altering the effector-target interaction, knocking out of host-susceptibility genes, engineering synthetic immune receptor eliciting broad spectrum resistance, uncoupling of antagonistic action of defense hormones etc. Alternatively, modification of insect genomes has been used either to create gene drive or to counteract resistance to various insecticides. The distinct advantage of genome editing system is that it can knock out specific target region in the genome without leaving the unwanted vector backbone. In this article, we have reviewed the novel opportunities offered by the genome editing technologies for developing insect and pathogen resistant crop-types, their future prospects and anticipated challenges.
Daisy-chain gene drives
5497MIT Media Lab, 2019-04-03 18:36:17.
Who should decide whether, when, and how to alter the environment? These are hard questions, especially when the decisions will impact people in many different communities or nations. Daisy drive systems may help by empowering local communities to make decisions concerning their local environments without imposing them on anyone else.
RISCOS BIOTECNOLÓGICOS AMBIENTAIS E PARTICIPAÇÃO SOCIAL: POR UMA GESTÃO DEMOCRÁTICA DA BIOTECNOLOGIA GENE DRIVE NA ATUAÇÃO DA CTNBIO
23872L. C. Rodrigues, Revista Jurídica (FURB), 22. 2019-03-15 09:15:24.
This research aims to study the way in which the environmental risks of Gene Drive biotechnology challenge forms of effective social participation, inserted in the management of biotechnological risks, whose responsibility lies with the organs linked to the State (CTNBio performance). The method of hypothetical-deductive approach, the method of topical and systematic juridical interpretation and the technique of bibliographic research were used. The conclusion reached was that the need to strengthen the objective sharing of information in an advisory manner to the general public in the face of Gene Drive's biotechnology risks within the framework of the CTNBio from the modification of the current Public Hearings legal model, which gives indications of omissions and lags before the complexity of the theme..
Genetic pest management technologies to control invasive rodents
11576D. Kanavy and D. Threadgill, Island invasives: scaling up to meet the challenge, 2019-03-05 15:20:05.
Many strategies exist to manage invasive pests on islands, ranging from poison to trapping, with varying degrees of success. Genetic technologies are increasingly being applied to insect pests, but so far, not to vertebrates. We are implementing a genetic strategy to eradicate invasive mouse populations as another tool for pest control. Mus musculus, the common house mouse, is one of the most widespread invasive species. Mice threaten human health, agriculture, and biodiversity on many islands, particularly seabirds. Seabirds are endangered indirectly through competition for resources or predators being attracted by the mice or directly with mice attacking chicks and eggs. Rodenticides are the most common method of eradicating mice, but their use leads to poisoning of non-target species and has limited efficacy against mice. An approach that could eliminate non-target species impact would be to engineer daughterless mice linked to a gene drive system for self-sustained propagation. For this project, we have investigated exploiting a naturally occurring gene drive, the t-complex. Using the t w2 haplotype of the t-complex, we observed the t w2 haplotype being transmitted to offspring with a transmission distortion ratio of 95.3%. The daughterless phenotype is being accomplished by inserting the Sry gene (male sex-determining gene) into an autosome containing the tw2 haplotype via CRISPR/Cas9 gene editing. The presence of Sry will induce testis formation, regardless of the sex chromosomes naturally inherited. When Sry is inserted into the t-complex, the desired gene will spread through the population, eliminating female offspring. This model system will support studies to evaluate the effectiveness of crashing an invasive population without adversely affecting other
Trialling gene drives to control invasive species: what, where and how?
11573T. Harvey-Samuel, K. J. Campbell, M. Edgington and L. Alphey, Island invasives: scaling up to meet the challenge, 2019-03-05 15:16:48.
The control of invasive species would be enhanced through the addition of novel, more effective and sustainable pest management methods. One control option yet to be trialled in the field is to deploy transgene-based ‘Gene Drives’: technologies which force the inheritance of a genetic construct through the gene pool of a wild population, suppressing it or replacing it with a less harmful form. There is considerable interest in applying gene drives to currently intractable invasives across a broad taxonomic range. However, not all species will make efficient or safe targets for these technologies. Additionally, the safety and efficacy of these systems will vary according to where they are deployed, the specific molecular design chosen, and how these factors interact with the ecology of the target pest. Given the transformative but also controversial nature of gene drives, it is imperative that their first field trials are able to successfully demonstrate that they can be used safely and efficiently. Here, we discuss how to maximise the probability of this outcome through considering three important questions: What types of invasive species should we use to trial gene drives? Where should we be trialling them? and How should these trials be conducted? In particular, we focus on the ecological, genetic and geographic features of small, isolated islands which make them ideal locations for these initial trials. A case study of an island invasive that is deemed highly appropriate for gene drive intervention, and for which gene drive development is currently underway (Mus musculus), is used to further explore these concepts
Towards a genetic approach to invasive rodent eradications: assessing reproductive competitiveness between wild and laboratory mice
11570M. Serr, N. Heard and J. Godwin, Island invasives: scaling up to meet the challenge, 2019-03-05 15:10:12.
House mice are significant invasive pests, particularly on islands without native mammalian predators. As part of a multi-institutional project aimed at suppressing invasive mouse populations on islands, we aim to create heavily male-biased sex ratios with the goal of causing the populations to crash. Effective implementation of this approach will depend on engineered F1 wild-lab males being effective secondary invaders that can mate successfully. As a first step in assessing this possibility, we are characterising genetic and behavioural differences between Mus musculus strains in terms of mating and fecundity using wild house mice derived from an invasive population on the Farallon Islands (MmF), a laboratory strain C57BL/6/129 (tw2), and F1 wild-lab off spring. Mice with the ‘t allele’ (tw2) have a naturally occurring gene drive system. To assess fertility in F1 wild-lab crosses, tw2 males were paired with wild-derived females from the Farallon Islands (MmF). Results of these matings indicate litter sizes are comparable but that weaned pup and adult wild-lab mice are heavier in mass. Next, we initiated tests of male competitiveness using larger (3 m2 ) enclosures with enrichment. We introduced both an MmF and a tw2-bearing male to two MmF females to assess mating outcomes. Preliminary results of these experiments show none of the offspring carried the t-allele. However, performing the same experiment with F1 wildlab males instead of a full lab background resulted in 70% of off spring carrying the t w2 allele. This indicates that F1 wildlab males may be able to successfully compete and secondarily invade. It will be important in subsequent experiments to determine what characteristics contribute to secondary invasion success. More generally, a better understanding of characteristics contributing to overall success in increasingly complex and naturalistic environments will be critical in determining the potential of a gene drive-based eradication approach for invasive mice on islands
A potential new tool for the toolbox: assessing gene drives for eradicating invasive rodent populations
11550K. J. Campbell, J. R. Saah, P. R. Brown, J. Godwin, F. Gould, G. R. Howald, A. Piaggio, P. Thomas, D. M. Tompkins, D. Threadgill, J. Delborne, D. Kanavy, T. Kuiken, H. Packard, M. Serr and A. Shiels, Island invasives: scaling up to meet the challenge, 2019-03-05 14:59:34.
Invasive rodents have significant negative impacts on island biodiversity. All but the smallest of rodent eradications currently rely on island-wide rodenticide applications. Although signifi cant advances have been made in mitigating unintended impacts, rodent eradication on inhabited islands remains extremely challenging. Current tools restrict eradication eff orts to fewer than 15% of islands with critically endangered or endangered species threatened by invasive rodents. The Genetic Biocontrol of Invasive Rodents partnership is an interdisciplinary collaboration to develop and evaluate gene drive technology for eradicating invasive rodent populations on islands. Technological approaches currently being investigated include the production of multiple strains of Mus musculus with a modifi ed form of the native t-complex, or a CRISPR gene drive, carrying genes or mechanisms that determine sex. These systems have the potential to skew the sex ratio of off spring to approach 100% single-sex, which could result in population collapse. One goal proposed is to test the ability of constructs to spread and increase in frequency in M. musculus populations in biosecure, captive settings and undertake modelling to inform development and potential deployment of these systems. Structured ecologically-based risk assessments are proposed, along with social and cultural engagement to assess the acceptability of releasing a gene drive system. Work will be guided by an external ethics advisory board. Partners are from three countries with significant regulatory capacity (USA, Australia, New Zealand). Thus, we will seek data sharing agreements so that results from experiments may be used within all three countries and treat regulatory requirements as a minimum. Species-specific, scalable, and socially acceptable new eradication tools could produce substantial biodiversity benefits not possible with current technologies. Gene drive innovation may provide such a tool for invasive species management and be potentially transformative and worthy of exploring in an inclusive, responsible, and ethical manner.
Modulating CRISPR gene drive activity through nucleocytoplasmic localization of Cas9 in S. cerevisiae
18839M. E. Goeckel, E. M. Basgall, I. C. Lewis, S. C. Goetting, Y. Yan, M. Halloran and G. C. Finnigan, Fungal Biology Biotechnology, 6:2. 2019-02-16 13:04:41.
In this study, we use artificial gene drives in budding yeast to explore mechanisms to modulate nuclease activity of Cas9 through its nucleocytoplasmic localization. We examine non-native nuclear localization sequences (both NLS and NES) on Cas9 fusion proteins in vivo through fluorescence microscopy and genomic editing. Our results demonstrate that mutational substitutions to nuclear signals and combinatorial fusions can both modulate the level of gene drive activity within a population of cells.
Gene drive technology makes mouse offspring inherit specific traits from parents
4531Cooper, KLG, Hannah A., The Conversation, 2019-01-24 00:00:00.
As mouse geneticists, we spend a lot of time waiting for mice to make more mice. Their small size, ease of care and willingness to mate have made mice the “mammal of choice” for scientists for more than a century. Indeed, these wriggly fur balls that strike fear in the hearts of some are owed a debt of gratitude for all they’ve taught researchers about human health and how mammalian bodies are built and function.
Gene drive tested in mice – Expert Reaction
4541Science Media Centre, Science Media Centre, 2019-01-24 00:00:00.
Using CRISPR genome editing, the researchers developed a process to make a gene more likely to be inherited than by chance alone. Their attempts with male mice were unsuccessful, but when it was used in females they increased the inheritance of the desired gene from 50 per cent to about 70 per cent, which they say might be enough for use in the lab.
Gene editing research highlights challenges in using CRISPR for pest control
4532Dreaver, C, Radio New Zealand, 2019-01-24 00:00:00.
US researchers have had some success in using the gene editing technique CRISPR to test out a gene drive in mice, to modify their genes - highlighting the challenges researchers face if it were to be used in pest eradication.
Tool for controlling genetic inheritance tested in mice for the first time
4535Hays, B, UPI, 2019-01-24 00:00:00.
With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, that are not currently possible, said researcher Kimberly Cooper.
Gene drive, a powerful way to speed genetic inheritance, shown for first time in mammals, UCSD researchers say
4533Fikes, BJ, San Diego Union Tribune, 2019-01-23 00:00:00.
Gene drive -- the ability to shortcut genetic inheritance by propelling a gene throughout a population -- has been demonstrated in principle for the first time in mammals.; ; UC San Diego scientists reported this feat in mice in a study released Wednesday in the journal Nature. It can be found at http://j.mp/ucsdgenedrive. A previous study from UCSD researchers demonstrated this feat in insects, also a first at its time
Gene Drives Work in Mice (if They’re Female)
4538Rennie, JC, Jordana, Quanta Magazine, 2019-01-23 00:00:00.
Conservationists and bioethicists often regard the packages of engineered DNA called “gene drives” with a mixture of wonder, excitement and dread. Gene drives violate the normal rules of inheritance by making sure they get passed down to all of their host organism’s offspring, not just to half of them; they therefore have the unnerving potential to rapidly and irrevocably alter a population. Much of the controversy about gene drives has centered on the practicality (and hubris) of using them to control dangerous insect pests, since insects were about the only animals in which gene drives had been shown to work.
La reacción genética en cadena llega a los mamíferos
4537Mediavilla, D, El Pais, 2019-01-23 00:00:00.
Un experimento muestra que la edición de los genes puede introducir cambios en especies completas que permitan incluso su extinción en un área geográfica
Researchers first to use CRISPR/Cas9 to control genetic inheritance in mice
4529University of California, Phys Org, 2019-01-23 00:00:00.
Biologists at the University of California San Diego have developed the world's first CRISPR/Cas9-based approach to control genetic inheritance in a mammal.
Scientists rewrite mice DNA so genes can be spread through species
4539Sample, I, The Guardian, 2019-01-23 00:00:00.
Controversial procedure has huge potential to combat diseases such as malaria
US scientists overturn genetic inheritance rules in lab mice
4530Cookson, C, Financial Times, 2019-01-23 00:00:00.
New gene drive technology that could revolutionise biology research has been demonstrated for the first time in mammals, after US scientists overturned the normal rules of genetic inheritance in laboratory mice.; ; Scientists at the University of California San Diego employed the technology to turn a group of lab mice white, using a complex DNA editing procedure that allowed a white-coat mutation to spread through successive generations of animals with unnatural speed.
Effective strategies for safeguarding CRISPR gene-drive experiments
4540ScienceDaily, ScienceDaily, 2019-01-22 00:00:00.
Researchers have demonstrated for the first time how two molecular strategies can safeguard CRISPR gene-drive experiments in the lab, according to a new study.
Gene drive mosquitoes and the new era of medical colonialism
4536Mayet, MC, L. I.; Sirinathsingji, E, GM Watch, 2019-01-22 00:00:00.
The highly contentious issue of gene drive technologies – a novel extreme form of genetic engineering designed to alter or even eradicate entire populations and species – was at the heart of the international negotiations at the biennial UN Biodiversity Conference held in Sharm el-Sheikh, Egypt, in November 2018.
An overview of OECD activities related to modern techniques of biotechnology and genome editing
3923Kearns, P, Transgenic Research, 28:41-44. 2019-01-21 00:00:00.
Since commercial use of genetically-engineered (genetically- modified) plants started in 1996, many agricultural products have been developed to improve crop traits. The foods and feeds derived from these commodities have drastically increased worldwide. However, answering health and environmental safety concerns associated with the agricultural use of biotechnology is essential in countries producing the products, as well as in countries using them. To address these concerns, the OECD conducts programmes of work for sharing information, developing tools to facilitate a harmonised approach of risk assessment, and contributing to building consensus between national authorities. This report provides background information on some OECD activities related to safety considerations associated with the use of biotechnology in agriculture (covering applications to crop plants, trees, animals, micro-organisms), including the recent emergence of genome editing techniques.
Does the U.S. public support using gene drives in agriculture? And what do they want to know?
3922Jones, MSD, Jason A.; Elsensohn, Johanna; Mitchell, Paul D.; Brown, Zachary S., Science Advances, 5:eaau8462. 2019-01-20 00:00:00.
Gene drive development is progressing more rapidly than our understanding of public values toward these technologies. We analyze a statistically representative survey (n = 1018) of U.S. adult attitudes toward agricultural gene drives. When informed about potential risks, benefits, and two previously researched applications, respondents’ support/opposition depends heavily (+22%/?19%) on whether spread of drives can be limited, non-native versus native species are targeted (+12%/?9%), or the drive replaces versus suppresses target species (±2%). The one-fifth of respondents seeking out non–GMO–labeled food are more likely to oppose drives, although their support exceeds opposition for limited applications. Over 62% trust U.S. universities and the Department of Agriculture to research gene drives, with the private sector and Department of Defense viewed as more untrustworthy. Uncertain human health and ecological effects are the public’s most important concerns to resolve. These findings can inform responsible innovation in gene drive development and risk assessment.
On the road to a gene drive in mammals
3902Conklin, BR, Nature, 566:43-45. 2019-01-20 00:00:00.
A method for making a version of a gene more likely to be inherited than normal, generating what is called a gene drive, might be used to control insect populations. It has now been reported to work in mammals, too.
CRISPR gene drive efficiency and resistance rate is highly heritable with no common genetic loci of large effect
3901Champer, JW, Z. X.; Luthra, A.; Reeves, R.; Chung, J.; Liu, C.; Lee, Y. L.; Liu, J. X.; Yang, E.; Messer, P. W.; Clark, A. G., Genetics, 212:333-341. 2019-01-19 00:00:00.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. Clustered regularly interspaced short palindromic repeat (CRISPR) homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population over time. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would eventually halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation postfertilization in the early embryo ranged from 7 to 79% among lines and averaged 42 +/- 18%. We performed a genome-wide association study using our results in the DGRP lines, and found that the resistance and conversion rates were not explained by common alleles of large effect, but instead there were several genetic polymorphisms showing weak association. RNA interference knockdown of several genes containing these polymorphisms confirmed their effect, but the small effect sizes imply that their manipulation would likely yield only modest improvements to the efficacy of gene drives.
Killing two bugs with one stone: a perspective for targeting multiple pest species by incorporating reproductive interference into sterile insect technique
3921Honma, AK, N.; Noriyuki, S., Pest Management Science, 75:571-577. 2019-01-19 00:00:00.
The sterile insect technique is an environmentally friendly method to control and even eradicate agricultural and veterinary insect pests without using chemical pesticides in excess. However, the continuous production and release of sterile insects is economically costly and eradication programs using sterile insects have not always been successful owing to the incomplete mating ability of the sterile insects. Here we focus on the theory and empirical findings of interspecific negative mating interaction, known as reproductive interference, to develop a more cost-effective and value-added pest management program. We suggest that sterile insects can be used for simultaneous control of both wild-type conspecifics and closely related pest species by taking advantage of the fact that, when species recognition abilities are incomplete, courtship and mating are often misdirected toward heterospecies. This new approach might help mitigate economic damage and human health crises caused by pest insects. (c) 2018 Society of Chemical Industry
MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations
3941Sánchez C, HMW, Sean L.; Bennett, Jared B.; Marshall, John M., Methods in Ecology and Evolution, 10:1-24. 2019-01-19 00:00:00.
Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. The advent of CRISPR/Cas9-based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has enabled a wide range of gene drive architectures to be realized, creating a need for their population-level and spatial dynamics to be explored. 2.We present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying userdefined inheritance patterns, b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pests, and c) a landscape module generates the metapopulation model by which insect populations are connected via migration over space. 3.Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9-based homing gene drive for: a) driving a disease-refractory gene into a population (i.e. population replacement), and b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing-resistant alleles in both cases. Further documentation and use examples are provided at the project's Github repository. 4.MGDrivE is an open-source R package freely available on CRAN. We intend the package to provide a flexible tool capable of modeling novel inheritance-modifying constructs as they are proposed and become available. The field of gene drive is moving very quickly, and we welcome suggestions for future development.
Molecular safeguarding of CRISPR gene drive experiments
3900Champer, JC, Joan; Lee, Yoo Lim; Liu, Chen; Yang, Emily; Wen, Zhaoxin; Clark, Andrew G.; Messer, Philipp W., eLife, 8:e41439. 2019-01-18 00:00:00.
CRISPR-based homing gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species. This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population. Here, we experimentally demonstrate the suitability of synthetic target site drives as well as split drives as flexible safeguarding strategies for gene drive experiments by showing that their performance closely resembles that of standard homing drives in Drosophila melanogaster. Using our split drive system, we further find that maternal deposition of both Cas9 and gRNA is required to form resistance alleles in the early embryo and that maternally-deposited Cas9 alone can power germline drive conversion in individuals that lack a genomic source of Cas9.
Population management using gene drive: molecular design, models ofspread dynamics and assessment of ecological risks
3940Rode, NOE, A.; Bourguet, D.; Courtier-Orgogozo, V.; Debarre, F., Conservation Genetics, 20:671-690. 2019-01-18 00:00:00.
CRISPR gene drive has recently been proposed as a promising technology for population management, including in conservation genetics. The technique would consist in releasing genetically engineered individuals that are designed to rapidly propagate a desired mutation or transgene into wild populations. Potential applications in conservation biology include the control of invasive pest populations that threaten biodiversity (eradication and suppression drives), or the introduction of beneficial mutations in endangered populations (rescue drives). The propagation of a gene drive is affected by different factors that depend on the drive construct (e.g. its fitness effect and timing of expression) or on the target species (e.g. its mating system and population structure). We review potential applications of the different types of gene drives for conservation. We examine the challenges posed by the evolution of resistance to gene drives and review the various molecular and environmental risks associated with gene drives (e.g. propagation to non target populations or species and unintended detrimental ecosystem impacts). We provide some guidelines for future gene drive research and discuss ethical, biosafety and regulation issues.
Gene drives as a response to infection and resistance
3919Hayirli, TCM, P.F., Infection and Drug Resistance, 12:229-234. 2019-01-17 00:00:00.
Vector-borne infectious diseases continue to be a major threat to public health. Although some prevention and treatment modalities exist for these diseases, resistance to such modalities, exacerbated by global climate change, remains a fundamental challenge. Developments in genomic engineering technologies present a new front in battling vector-borne illnesses; however, there is a lack of consensus over the scope and consequences of these approaches. In this article, we use malaria as a case study to address the developments and controversies surrounding gene drives, a novel genomic engineering technology. We draw attention to the themes of infection control, resistance, and reversibility using a science and technology studies framework. Unlike other current prevention and treatment modalities, gene drives have the capacity to alter not only single organisms but also entire species and ecologies. Therefore, broader public and scientific engagement is needed to inform a more inclusive discussion between clinicians, researchers, policy makers, and society.
Male competition and the evolution of mating and ire-history traits in experimental populations of Aedes aegypti
3939Qureshi, AA, A.; Hollis, B.; Ponlawat, A.; Cator, L. J., Proceedings of the Royal Society B-Biological Sciences, 286:20190591. 2019-01-17 00:00:00.
Aedes aegypti is an important disease vector and a major target of reproductive control efforts. We manipulated the opportunity for sexual selection in populations of Ae. aegypti by controlling the number of males competing for a single female. Populations exposed to higher levels of male competition rapidly evolved higher male competitive mating success relative to populations evolved in the absence of competition, with an evolutionary response visible atter only five generations. We also detected correlated evolution in other important mating and life-history traits, such as acoustic signalling, fecundity and body size. Our results indicate that there is ample segregating variation for determinants of male mating competitiveness in wild populations and that increased male mating success trades-off with other important life-history traits. The mating conditions imposed on laboratory-reared mosquitoes are likely a significant determinant of male mating success in populations destined for release.
Variability in the durability of CRISPR-Cas immunity
3899Chabas, HN, A.; Meaden, S.; Westra, E. R.; Tremblay, D. M.; Pradier, L.; Lion, S.; Moineau, S.; Gandon, S., Philosophical Transactions of the Royal Society B-Biological Sciences, 374:1-9. 2019-01-17 00:00:00.
The durability of host resistance is challenged by the ability of pathogens to escape the defence of their hosts. Understanding the variability in the durability of host resistance is of paramount importance for designing more effective control strategies against infectious diseases. Here, we study the durability of various clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas) alleles of the bacteria Streptococcus thermophilus against lytic phages. We found substantial variability in durability among different resistant bacteria. Since the escape of the phage is driven by a mutation in the phage sequence targeted by CRISPR-Cas, we explored the fitness costs associated with these escape mutations. We found that, on average, escape mutations decrease the fitness of the phage. Yet, the magnitude of this fitness cost does not predict the durability of CRISPR-Cas immunity. We contend that this variability in the durability of resistance may be because of variations in phage mutation rate or in the proportion of lethal mutations across the phage genome. These results have important implications on the coevolutionary dynamics between bacteria and phages and for the optimal deployment of resistance strategies against pathogens and pests. Understanding the durability of CRISPR-Cas immunity may also help develop more effective gene-drive strategies based on CRISPR-Cas9 technology. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.
A Y-chromosome shredding gene drive for controlling pest vertebrate populations
3938Prowse, TAAA, F.; Cassey, P.; Thomas, P.; Ross, J. V., eLife, 8:19. 2019-01-16 00:00:00.
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that 'shreds' the Y chromosome, thereby converting XY males into fertile XO females. Firstly, we demonstrate that the CRISPR/Cas12a system can eliminate the Y chromosome in embryonic stem cells with high efficiency (c. 90%). Next, using stochastic, individual-based models of a pest mouse population, we show that a Y-shredding drive that progressively depletes the pool of XY males could effect population eradication through mate limitation. Our molecular and modeling data suggest that a Y-CHOPE gene drive could be a viable tool for vertebrate pest control.
Gene drive gone wild: exploring deliberative possibilities by developing One Health ethics
3898Capps, B, Law, Innovation and Technology, 11:231-256. 2019-01-16 00:00:00.
Gene editing may be used to engineer organisms that are better or worse adapted to survival. Coupled with gene drives ? molecular genetic strategies that perpetuate specific phenotypes in a target species ? it would now be possible to edit wild animal populations that impact on public health. It is generally agreed that community engagement should guide prospective gene drive field trials. However, the analysis in this article reveals that there is a tension between publics and the public interest: it is contentious to allow communities to decide policy when doing so will have consequences beyond their own interests, as surely gene drives will; conversely, it goes against ideal deliberation for the state to impose policy without this democratic condition. The gene drive controversy creates further dichotomies illustrative of this tension: giving effect to weighted decisions that discriminate between culture and nature, local and global, private and public, and present and future interests. In this article, an emerging concept of One Health ethics (OH) is employed to strengthen ethical engagement on the policy roadmap used to navigate the gene drive controversy. OH in practice has been shown to provide insightful solutions at the interface between animal and human health; and, in this article, that advantage is extended to the public good and public interest. In so doing, OH ethics ? as spelled out here ? is coextensive with public health ethics.
Knowledge engagement in gene drive research for malaria control
3918Hartley, ST, D.; Ledingham, K.; Coulibaly, M.; Diabate, A.; Dicko, B.; Diop, S.; Kayondo, J.; Namukwaya, A.; Nourou, B.; Toe, L. P., PLOS Neglected Tropical Diseases, 13:e0007233. 2019-01-16 00:00:00.
Scientists and funding bodies have made repeated calls for public engagement in gene drive. In 2016, the National Academies of Sciences, Engineering, and Medicine (NASEM) published its report, Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values. The report identified public engagement as a key area of responsible science, defining engagement as “seeking and facilitating the sharing and exchange of knowledge, perspectives, and preferences between or among groups who often have differences in expertise, power, and values”. Researchers are asked to participate in two-way engagement with publics (defined as stakeholders, communities, and the public) to allow their knowledge to contribute to technology development and align the technology with public values. In this viewpoint, we share our initial research findings in this area and propose a conceptual tool that contributes to the debate at this critical juncture.
Dr. Kevin Esvelt, MIT | Gene Drive
5482iBiology, 2019-01-15 18:05:30.
Dr. Kevin Esvelt explains how CRISPR-based gene drives can be used to spread genetic alterations through wild populations. He discusses strategies to maximize benefit and minimize risk.
Safe CRISPR: Challenges and Possible Solutions
3937Pineda, ML, A.; Collins, J. P.; Kiani, S., Trends in Biotechnology, 37:389-401. 2019-01-15 00:00:00.
Applications of CRISPR in human health and in gene drives are at the forefront of biological research as tools. This technology will affect humankind and our environment, so as this technology pushes forward, the design and implementation of safety measures is imperative. Novel technologies and forethought in various applications of CRISPR are essential for using this technology safely. Here, we review environmental and health-related safety concerns associated with using CRISPR and ways proposed to minimize risk.
Design, execution, and analysis of CRISPR-Cas9-based deletions and genetic interaction networks in the fungal pathogen Candida albicans
3916Halder, VP, C. B. M.; Chavez, A.; Shapiro, R. S., Nature Protocols, 14:955-975. 2019-01-14 00:00:00.
The study of fungal pathogens is of immediate importance, yet progress is hindered by the technical challenges of genetic manipulation. For Candida species, their inability to maintain plasmids, unusual codon usage, and inefficient homologous recombination are among the obstacles limiting efficient genetic manipulation. New advances in genomic biotechnologies -particularly CRISPR-based tools-have revolutionized genome editing for many fungal species. Here, we present a protocol for CRISPR-Cas9-based manipulation in Candida albicans using a modified gene-drive-based strategy that takes similar to 1 month to complete. We detail the generation of Candida-optimized Cas9-based plasmids for gene deletion, an efficient transformation protocol using C. albicans haploids, and an optimized mating strategy to generate homozygous single- and double-gene diploid mutants. We further describe protocols for quantifying cell growth and analysis pipelines to calculate fitness and genetic interaction scores for genetic mutants. This protocol overcomes previous limitations associated with genetic manipulation in C. albicans and advances researchers' ability to perform genetic analysis in this pathogen; the protocol also has broad applicability to other mating-competent microorganisms.
Population genetics of Anopheles funestus, the African malaria vector, Kenya
3936Ogola, EOO, J. O.; Mwangangi, J. M.; Masiga, D. K.; Tchouassi, D. P., Parasites & Vectors, 12:15. 2019-01-14 00:00:00.
Anopheles funestus is among the major malaria vectors in Kenya and sub-Saharan Africa and has been recently implicated in persistent malaria transmission. However, its ecology and genetic diversity remain poorly understood in Kenya.MethodsUsing 16 microsatellite loci, we examined the genetic structure of An. funestus sampled from 11 locations (n = 426 individuals) across a wide geographical range in Kenya spanning coastal, western and Rift Valley areas.ResultsKenyan An. funestus resolved as three genetically distinct clusters. The largest cluster (FUN1) broadly included samples from western and Rift Valley areas of Kenya with two clusters identified from coastal Kenya (FUN2 and FUN3), not previously reported. Geographical distance had no effect on population differentiation of An. funestus. We found a significant variation in the mean Plasmodium infectivity between the clusters ((2) = 12.1, df = 2, P = 0.002) and proportional to the malaria prevalence in the different risk zones of Kenya. Notably, there was variation in estimated effective population sizes between the clusters, suggesting possible differential impact of anti-vector interventions in represented areas.ConclusionsHeterogeneity among Kenyan populations of An. funestus will impact malaria vector control with practical implications for the development of gene-drive technologies. The difference in Plasmodium infectivity and effective population size between the clusters could suggest potential variation in phenotypic characteristics relating to competence or insecticide resistance. This is worth examining in future studies.
Spatial structure undermines parasite suppression by gene drive cargo
3896Bull, JJR, Christopher H.; Gomulkiewicz, Richard; Krone, Stephen M., PeerJ, 7:e7921. 2019-01-14 00:00:00.
Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.
CRISPR in sub-Saharan Africa: Applications and education
3935Ogaugwu, CEA, S. O.; Adekoya, M. A., Trends in Biotechnology, 37:234-237. 2019-01-13 00:00:00.
Clustered regularly interspaced shortpalindromicrepeats (CRISPR) technology has enabled genetic engineering feats previously considered impracticable, offering great hopes for solutions to problems facing society. We consider it timely to highlight how CRISPR can benefit public health, medicine, and agriculture in sub-Saharan Africa (SSA) and offer recommendations for successful implementation.
Efficient allelic-drive in Drosophila
3915Guichard, AH, T.; Bobik, M.; Xu, X. R. S.; Klanseck, C.; Kushwah, R. B. S.; Berni, M.; Kaduskar, B.; Gantz, V. M.; Bier, E., Nature Communications, 10:1640. 2019-01-13 00:00:00.
Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a nonpreferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as "shadow-drive", have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox.
Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs
3895Buchman, AG, S.; Li, M.; Antoshechkin, I.; Li, H. H.; Wang, H. W.; Chen, C. H.; Klein, M. J.; Duchemin, J. B.; Paradkar, P. N.; Akbari, O. S., Proceedings of the National Academy of Sciences of the United States of America, 116:3656-3661. 2019-01-13 00:00:00.
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.
Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive
3934Oberhofer, GI, T.; Hay, B. A., Proceedings of the National Academy of Sciences of the United States of America, 116:6250-6259. 2019-01-12 00:00:00.
There is great interest in being able to spread beneficial traits throughout wild populations in ways that are self-sustaining. Here, we describe a chromosomal selfish genetic element, CleaveR [Cleave and Rescue (ClvR)], able to achieve this goal. ClvR comprises two linked chromosomal components. One, germline-expressed Cas9 and guide RNAs (gRNAs)-the Cleaver-cleaves and thereby disrupts endogenous copies of a gene whose product is essential. The other, a recoded version of the essential gene resistant to cleavage and gene conversion with cleaved copies-the Rescue-provides essential gene function. ClvR enhances its transmission, and that of linked genes, by creating conditions in which progeny lacking ClvR die because they have no functional copies of the essential gene. In contrast, thosewho inherit ClvR survive, resulting in an increase in ClvR frequency. ClvR is predicted to spread to fixation under diverse conditions. To test these predictions, we generated a ClvR element in Drosophilamelanogaster. ClvRtko is located on chromosome 3 and uses Cas9 and four gRNAs to disrupt melanogaster technical knockout (tko), an X-linked essential gene. Rescue activity is provided by tko from Drosophila virilis. ClvRtko results in germline and maternal carryover-dependent inactivation of melanogaster tko (> 99% per generation); lethality caused by this loss is rescued by the virilis transgene; ClvRtko activities are robust to genetic diversity in strains from five continents; and uncleavable but functional melanogaster tko alleles were not observed. Finally, ClvRtko spreads to transgene fixation. The simplicity of ClvR suggests it may be useful for altering populations in diverse species.
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9-mediated mutagenesis of the multiple edematous wings gene induces muscle weakness and flightlessness in Bactrocera dorsalis (Diptera: Tephritidae)
3954Zheng, WL, Q.; Sun, H.; Ali, M. W.; Zhang, H., Insect Molecular Biology, 28:222-234. 2019-01-12 00:00:00.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system is a versatile, efficient and heritable gene editing tool that can be useful for genome engineering. Bactrocera dorsalis (Hendel) is a major pest of agriculture that causes great economic losses. We used the B. dorsalis multiple edematous wings (Bdmew) gene as the target gene to explore the effectiveness of CRISPR/Cas9 for B. dorsalis genome manipulation. We studied the physiological functions of the Bdmew gene, particularly those related to muscle development. Site-specific genome editing was feasible using direct microinjection of specific guide RNA and the Cas9-plasmid into B. dorsalis embryos. Mutation frequencies ranged from 12.1 to 30.2% in the injected generation. Mosaic G0, with the mew mutation, was heritable to the next generation. The G1 displayed a series of defective phenotypes including muscle weakness, flightlessness, failure to eclose, wing folds and unbalanced movement. These results demonstrated that CRISPR/Cas9 can act as a highly specific, efficient, heritable tool for genome manipulation in B. dorsalis and this has significance for gene function research and genetic control of pests. The Bdmew gene possesses key functions in muscle development of B. dorsalis. Bdmew mutations cause a series of serious defects by interfering with muscle development and may provide a means for controlling B. dorsalis via a gene-based method such as gene drive.
CRISPR in Parasitology: Not Exactly Cut and Dried!
3894Bryant, JMB, S.; Glover, L.; Hutchinson, S.; Rachidi, N., Trends in Parasitology, 35:409-422. 2019-01-12 00:00:00.
CRISPR/Cas9 technology has been developing rapidly in the field of parasitology, allowing for the dissection of molecular processes with unprecedented efficiency. Optimization and implementation of a new technology like CRISPR, especially in nonmodel organisms, requires communication and collaboration throughout the field. Recently, a 'CRISPR in Parasitology' symposium was held at the Institut Pasteur Paris, bringing together scientists studying Leishmania, Plasmodium, Trypanosoma, and Anopheles. Here we share technological advances and challenges in using CRISPR/Cas9 in the parasite and vector systems that were discussed. As CRISPR/Cas9 continues to be applied to diverse parasite systems, the community should now focus on improvement and standardization of the technique as well as expanding the CRISPR toolkit to include Cas9 alternatives/derivatives for more advanced applications like genome-wide functional screens.
Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline
3914Grunwald, HAG, V. M.; Poplawski, G.; Xu, X. R. S.; Bier, E.; Cooper, K. L., Nature, 566:105-109. 2019-01-12 00:00:00.
A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of CRISPR-Cas9 and endogenous homology-directed repair mechanisms to convert heterozygous genotypes to homozygosity(1-4). If implemented in laboratory rodents, similar systems would enable the rapid assembly of currently impractical genotypes that involve multiple homozygous genes (for example, to model multigenic human diseases). To our knowledge, however, such a system has not yet been demonstrated in mammals. Here we use an active genetic element that encodes a guide RNA, which is embedded in the mouse tyrosinase (Tyr) gene, to evaluate whether targeted gene conversion can occur when CRISPR-Cas9 is active in the early embryo or in the developing germline. Although Cas9 efficiently induces double-stranded DNA breaks in the early embryo and male germline, these breaks are not corrected by homology-directed repair. By contrast, Cas9 expression limited to the female germline induces double-stranded breaks that are corrected by homology-directed repair, which copies the active genetic element from the donor to the receiver chromosome and increases its rate of inheritance in the next generation. These results demonstrate the feasibility of CRISPR-Cas9-mediated systems that bias inheritance of desired alleles in mice and that have the potential to transform the use of rodent models in basic and biomedical research.
CRISPR-Cas9. The greatest advancement in genetic edition techniques requires an ethical reflection
3913Gomez-Tatay, LA, J., Cuadernos De Bioetica, 30:171-185. 2019-01-11 00:00:00.
The adaptation of the CRISPR system as a genetic editing tool has led to a revolution in many fields of application, as this technique is considerably faster, easier to perform and more efficient than predecessor techniques. However, some of these applications raise objective ethical issues that must be addressed. In this paper we discuss, based on the most recent data, the different issues related to CRISPR applications on the germ line, its introduction in clinical trials, the genetic edition of animals and plants for human consumption and the novel gene drive.
Efficient somatic and germline genome engineering of Bactrocera dorsalis by the CRISPR/Cas9 system
3953Zhao, STX, Z. Z.; Liu, Z. G.; Liu, Y. H.; Liu, X. R.; Chen, Z.; Li, J. H.; Yan, R. H., Pest Management Science, 75:1921-1932. 2019-01-11 00:00:00.
Bactrocera dorsalis (Hendel), a very destructive insect pest of many fruits and vegetables, is widespread in many Asian countries. To facilitate control of this pest, it is essential to investigate its genetics and gene function using targeted gene disruption. RESULTS Here, we describe successful targeted mutagenesis of the white and transformer genes in B. dorsalis through use of the clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) system. Co-injection of the white sgRNA and Cas9 mRNA into B. dorsalis embryos caused eye color change, and the white mutations in the germline were heritable. CRISPR-mediated knockout of the sex determination gene transformer (tra) in B. dorsalis resulted in a male-biased sex ratio and adult flies with abnormal outer and interior reproductive organs. Small indels and substitutions were induced by CRIRPR for both genes. CONCLUSION Our data demonstrate that somatic and germline genome engineering of the pest B. dorsalis can be performed efficiently using the CRISPR/Cas9 system, opening the door to the use of the CRISPR-mediated method for functional annotations of genes in B. dorsalis and for its population control using, for example, such as gene drive. (c) 2018 Society of Chemical Industry
Modelling the potential of genetic control of malaria mosquitoes at national scale
3933North, ARB, Austin; Godfray, H. Charles J., BMC Biology, 17:26. 2019-01-11 00:00:00.
The persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore the potential of using a driving-Y chromosome to suppress vector populations in a 106 km2 area of West Africa including all of Burkina Faso.
A genetic system for biasing the sex ratio in mice
3952Yosef, IEB, Liat; Globus, Rea; Shlomovitz, Inbar; Munitz, Ariel; Gerlic, Motti; Qimron, Udi, EMBO reports, 20:e48269. 2019-01-10 00:00:00.
Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a genetic system in mammals by crossing two genetically engineered mouse lines. The maternal line encodes a functional Cas9 protein on an autosomal chromosome, whereas the paternal line encodes guide RNAs on the Y chromosome targeting vital mouse genes. After fertilization, the presence of both the Y-encoded guide RNAs from the paternal sperm and the Cas9 protein from the maternal egg targets the vital genes in males. We show that these genes are specifically targeted in males and that this breeding consequently self-destructs solely males. Our results pave the way for a genetic system that allows biased sex production of livestock.
Daisy-chain gene drives for the alteration of local populations
3932Noble, CM, J.; Olejarz, J.; Buchthal, J.; Chavez, A.; Smidler, A. L.; DeBenedictis, E. A.; Church, G. M.; Nowak, M. A.; Esvelt, K. M., Proceedings of the National Academy of Sciences of the United States of America, 116:8275-8282. 2019-01-10 00:00:00.
If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, we detail a self-exhausting form of CRISPR-based drive system comprising genetic elements arranged in a daisy chain such that each drives the next. "Daisydrive" systems can locally duplicate any effect achievable by using an equivalent self-propagating drive system, but their capacity to spread is limited by the successive loss of nondriving elements from one end of the chain. Releasing daisy-drive organisms constituting a small fraction of the local wild population can drive a useful genetic element nearly to local fixation for a wide range of fitness parameters without self-propagating spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionarily stable daisy drive as well as self-propagating CRISPR-based gene drive. Especially when combined with threshold dependence, daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.
Precision control of CRISPR-Cas9 using small molecules and light
3912Gangopadhyay, SAC, K. J.; Manna, D.; Lim, D.; Maji, B.; Zhou, Q. X.; Choudhary, A., Biochemistry, 58:234-244. 2019-01-10 00:00:00.
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas system is an adaptive immune system of bacteria that has furnished several RNA-guided DNA endonucleases (e.g., Cas9) that are revolutionizing the field of genome engineering. Cas9 is being used to effect genomic alterations as well as in gene drives, where a particular trait may be propagated through a targeted species population over several generations. The ease of targeting catalytically impaired Cas9 to any genomic loci has led to development of technologies for base editing, chromatin imaging and modeling, epigenetic editing, and gene regulation. Unsurprisingly, Cas9 is being developed for numerous applications in biotechnology and biomedical research and as a gene therapy agent for multiple pathologies. There is a need for precise control of Cas9 activity over several dimensions, including those of dose, time, and space in these applications. Such precision controls, which are required of therapeutic agents, are particularly important for Cas9 as off-target effects, chromosomal translocations, immunogenic response, genotoxicity, and embryonic mosaicism are observed at elevated levels and with prolonged activity of Cas9. Here, we provide a perspective on advances in the precision control of Cas9 over aforementioned dimensions using external stimuli (e.g., small molecules or light) for controlled activation, inhibition, or degradation of Cas9.
CRISPR ethics: Moral considerations for applications of a powerful tool
3891Brokowski, C. and Adli, M., Journal of Molecular Biology, 431:88-101. 2019-01-09 00:00:00.
With the emergence of CRISPR technology, targeted editing of a wide variety of genomes is no longer an abstract hypothetical, but occurs regularly. As application areas of CRISPR are exceeding beyond research and biomedical therapies, new and existing ethical concerns abound throughout the global community about the appropriate scope of the systems' use. Here we review fundamental ethical issues including the following: 1) the extent to which CRISPR use should be permitted; 2) access to CRISPR applications; 3) whether a regulatory framework(s) for clinical research involving human subjects might accommodate all types of human genome editing, including editing of the germline; and 4) whether international regulations governing inappropriate CRISPR utilization should be crafted and publicized. We conclude that moral decision making should evolve as the science of genomic engineering advances and hold that it would be reasonable for national and supranational legislatures to consider evidence-based regulation of certain CRISPR applications for the betterment of human health and progress. (C) 2018 Published by Elsevier Ltd.
CRISPR-Clear: A fieldable detection procedure for potential CRISPR-Cas9 gene drive based bioweapons.
3931Nieuwenweg, ACvG, Martijn M.; Horsting, Angelina; Hegge, Jorrit W; Velders, Aldrik; Saggiomo, Vittorio, ChemRxiv, 2019:1-11. 2019-01-09 00:00:00.
Rapid progression in genetic modification research has made gene editing increasingly cheaper and easier to use. CRISPR-Cas9 for example, allows for the specific alteration of the genome of an organism with relative simplicity and low costs. This raised a worrying question; can genetic modification techniques be used to create novel bioweapons? A specific scenario is the initiation of a synthetic gene drive for malicious purposes. A synthetic gene drive can be used to quickly spread a mutation through an entire population. This mutation could alter vectors in such a way that they will spread human diseases or eradicate essential organisms. Since a gene drive spreads efficiently through a population, timely detection is essential. Thus, a quick and field deployable screening method is needed to counteract the malicious use of gene drives.; ; Here, we show a battery-operated, sensitive screening method, named CRISPR-Clear, for the detection of gene drive modified organisms. CRISPR-Clear is based on the combination of three components: 1) A DNA amplification technique known as loop-mediated isothermal amplification (LAMP) for detecting the presence of a gene drive; b) a portable battery-operated Arduino device which heats up the sample to allow DNA amplification, and c) a naked-eye visualization of the results.; ; We designed and tested six LAMP primers targeting a Cas9 endonuclease-based gene drive, assembled a battery-operated Arduino device and tested the naked-eye visualization method. In addition, we were able to detect the presence of the Cas9 gene, extracted from a transformed bacteria, providing a proof-of-concept of the CRISPR-Clear device.
Stakeholder attitudes towards the use of recombinant technology to manage the impact of an invasive species: Sea Lamprey in the North American Great Lakes
3951Thresher, REJ, M.; Drake, D. A. R., Biological Invasions, 21:575-586. 2019-01-09 00:00:00.
Several factors, including: (1) on-going difficulties of cost-effectively managing invasive species; (2) recent successes in using recombinant genetics to suppress mosquito populations; and, (3) developments in gene-drive technology, have re-invigorated interest in using genetic biotechnology to manage the impacts of invasive species. However, the extent to which there is social license' to develop and use these technologies has not been widely canvassed. We surveyed stakeholders involved directly and indirectly in managing Sea Lamprey (Petromyzon marinus) in the upper North American Great Lakes and a key community group of resource usersrecreational fishersto assess their support and concerns about researching, developing, and potentially implementing recombinant methods that an expert group assessed as likely to be effective in managing Sea Lamprey in the Great Lakes. Both groups overwhelmingly supported initiating R&D and, if risks were deemed very low, undertaking steps towards implementation. The key concern expressed by both groups was the risk of impacts to non-target taxa, including valued native populations of Sea Lamprey outside of the Great Lakes. Few respondents expressed opposition based on ethical or moral grounds, which contrasts with previous surveys on the use of recombinant technology in general. The broad support for R&D into recombinant approaches is likely to reflect trust in the nominated implementing agency (the Great Lakes Fishery Commission), its history of extensive consultation prior to undertaking management actions, and the hope that genetic biocontrol could solve the Sea Lamprey problem rather than simply managing it.
A Question of Consent: Exterminator Mosquitoes in Burkina Faso
5538ETC group, 2019-01-08 20:10:07.
Target Malaria’s planned release of GMO mosquitos is step toward release of gene drive mosquitoes, a high-risk technology aimed at the elimination of entire species. Hundreds of organizations have demanded a moratorium on the use of this technology outside of strictly-controlled laboratories.
Integral gene drives for population replacement
3930Nash, AU, Giulia Mignini; Beaghton, Andrea K.; Hoermann, Astrid; Papathanos, Philippos Aris; Christophides, George K.; Windbichler, Nikolai, Biology Open, 8:bio037762. 2019-01-08 00:00:00.
A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population, while drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy.
Large-cage assessment of a transgenic sex-ratio distortion strain on populations of an African malaria vector
3910Facchinelli, LN, A.; Collins, C.; Menichelli, M.; Persampieri, T.; Bucci, A.; Spaccapelo, R.; Crisanti, A.; Benedict, M., Parasites & Vectors, 12:70. 2019-01-08 00:00:00.
Novel transgenic mosquito control methods require progressively more realistic evaluation. The goal of this study was to determine the effect of a transgene that causes a male-bias sex ratio on Anopheles gambiae target populations in large insectary cages. Life history characteristics of Anopheles gambiae wild type and Ag(PMB)1 (aka (gfp)124L-2) transgenic mosquitoes, whose progeny are 95% male, were measured in order to parameterize predictive population models. Ag(PMB)1 males were then introduced at two ratios into large insectary cages containing target wild type populations with stable age distributions and densities. The predicted proportion of females and those observed in the large cages were compared. A related model was then used to predict effects of male releases on wild mosquitoes in a west African village. The frequency of transgenic mosquitoes in target populations reached an average of 0.44 +/- 0.02 and 0.56 +/- 0.02 after 6 weeks in the 1:1 and in the 3:1 release ratio treatments (transgenic male:wild male) respectively. Transgenic males caused sex-ratio distortion of 73% and 80% males in the 1:1 and 3:1 treatments, respectively. The number of eggs laid in the transgenic treatments declined as the experiment progressed, with a steeper decline in the 3:1 than in the 1:1 releases. The results of the experiment are partially consistent with predictions of the model; effect size and variability did not conform to the model in two out of three trials, effect size was over-estimated by the model and variability was greater than anticipated, possibly because of sampling effects in restocking. The model estimating the effects of hypothetical releases on the mosquito population of a West African village demonstrated that releases could significantly reduce the number of females in the wild population. The interval of releases is not expected to have a strong effect. The biological data produced to parameterize the model, the model itself, and the results of the experiments are components of a system to evaluate and predict the performance of transgenic mosquitoes. Together these suggest that the Ag(PMB)1 strain has the potential to be useful for reversible population suppression while this novel field develops.
Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016–2018
3950Teem, JLA, Aggrey; Glover, Barbara; Ouedraogo, Jeremy; Makinde, Diran; Roberts, Andrew, Malaria Journal, 18:347. 2019-01-08 00:00:00.
Gene drive mosquitoes have been proposed as a possible means to reduce the transmission of malaria in Africa. Because this technology has no prior use-history at this time, environmental risk assessments for gene drive mosquitoes will benefit from problem formulation—an organized and ordered process to identify protection goals and potential pathways to harm to the environment, or animal or human health. Recognizing this need, the New Partnership for Africa’s Development (NEPAD), with support from African and international partners, organized four regional consultative workshops in Africa to initiate this process.
Conserving New Zealand’s native fauna: a review of tools being developed for the Predator Free 2050 programme
3929Murphy, ECR, J. C.; Broome, K. G.; Ryan, G. J.; Dowding, J. E., Journal of Ornithology, 160:883-892. 2019-01-07 00:00:00.
The endemic fauna of New Zealand evolved in the absence of mammalian predators and the introduction of the latter has been devastating. There have been numerous avian extinctions and 80% of the extant native avian taxa are currently threatened or at risk of extinction. Declines continue, and a fundamental change in predator management is required. In 2016 came the announcement of the ambitious Predator Free 2050 (PF 2050) programme, which aims to eradicate rats, mustelids, and Brushtail Possums from New Zealand by 2050. This paper reviews some of the many techniques being discussed or developed to implement the programme. Existing techniques are being refined and new tools are being developed. Research on new toxins, including those with potentially higher species specificity, is under way, and novel baits and toxin-delivery devices are being developed. Existing trap designs are being refined, and new self-resetting traps capable of multiple kills have been developed. Research is also under way on new lures and repellents. Eradications may be achieved in stages, and barriers (both natural and artificial) will be needed to protect areas already cleared. Current techniques will probably be inadequate to effect nationwide eradications, and new tools (possibly based on genetic technologies) will probably be required. Regulatory hurdles will need to be overcome, and community consultation and support (social licence) will be required throughout the programme. The use of some new technologies may be contentious, and not every new idea will necessarily be adopted. Technical, social, and organisational challenges exist, and national and international collaboration will be required for PF 2050 to succeed.
Modeling the mutation and reversal of engineered underdominance gene drives
3909Edgington, MPA, Luke S., Journal of Theoretical Biology, 479:14-21. 2019-01-07 00:00:00.
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, is based on the introduction of two independently segregating transgenic constructs each carrying a lethal gene, a suppressor for the lethal at the other locus and a desirable genetic “cargo”. Under this system individuals carrying at least one copy of each construct (or no copies of either) are viable whilst those that possess just one of the transgenic constructs are non-viable. Previous theoretical work has explored various properties of these systems, concluding that they should persist indefinitely in absence of resistance or mutation. Here we study a population genetics model of UD gene drive that relaxes past assumptions by allowing for loss-of-function mutations in each introduced gene. We demonstrate that mutations are likely to cause UD systems to break down, eventually resulting in the elimination of introduced transgenes. We then go on to investigate the potential of releasing “free suppressor” carrying individuals as a new method for reversing UD gene drives and compare this to the release of wild-types; the only previously proposed reversal strategy for UD. This reveals that while free suppressor carrying individuals may represent an inexpensive reversal strategy due to extremely small release requirements, they are not able to return a fully wild-type population as rapidly as the release of wild-types.
The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications
3889Beckmann, JFB, Manon; Chen, Hongli; Hochstrasser, Mark; Poinsot, Denis; Merçot, Hervé; Weill, Mylène; Sicard, Mathieu; Charlat, Sylvain, Trends in Genetics, 35:175-185. 2019-01-07 00:00:00.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin–antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.
Gene drive for population genetic control: non-functional resistance and parental effects
3888Beaghton, AKH, Andrew; Nolan, Tony; Crisanti, Andrea; Burt, Austin, Proceedings of the Royal Society B: Biological Sciences, 286:20191586. 2019-01-06 00:00:00.
Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.
Governing extinction in the era of gene editing
3928Monast, JJ, North Carolina Law Review, 97:1329-1358. 2019-01-06 00:00:00.
CRISPR-Cas9 genome-editing technology (“CRISPR”) offers a potential solution for some of the world’s critical conservation challenges. Scientists are harnessing CRISPR to expand genetic diversity of endangered species, control invasive species, or enhance species’ resiliency to a changing climate. Recreating extinct species is now realistic, as is engineering entirely new species. CRISPR also creates opportunities to address vector-borne infectious diseases such as malaria, dengue fever, and Zika using gene drive techniques that can spread genetic alterations through populations. ; While CRISPR is a powerful tool to address public health and conservation goals, it could allow scientists to bypass longstanding value choices underlying national and international conservation efforts and foster permanent ecosystem impacts before public policy can react. This Article argues that, while current conservation laws do not directly address many of the specific questions that arise with CRISPR, the Endangered Species Act (“ESA”) establishes a framework that can, and should, guide the use of gene editing. The proposal calls for: (1) a presumption against the release of genetically modified organisms that could cause species extinction, (2) exemptions for specific public health and environmental goals, and (3) updates to the ESA to clarify oversight of gene editing.
Locally Fixed Alleles: A method to localize gene drive to island populations
3948Sudweeks, JH, Brandon; Blondel, Dimitri V.; Campbell, Karl J.; Dhole, Sumit; Eisemann, John D.; Edwards, Owain; Godwin, John; Howald, Gregg R.; Oh, Kevin P.; Piaggio, Antoinette J.; Prowse, Thomas A. A.; Ross, Joshua V.; Saah, J. Royden; Shiels, Aaron B.; Thomas, Paul Q.; Threadgill, David W.; Vella, Michael R.; Gould, Fred; Lloyd, Alun L., Scientific Reports, 9:15821. 2019-01-06 00:00:00.
Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.
Controlling invasive rodents via synthetic gene drive and the role of polyandry
3927Manser, AC, S. J.; Sutter, A.; Blondel, D. V.; Serr, M.; Godwin, J.; Price, T. A. R., Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-01-05 00:00:00.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three-to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.
Gene drives in plants: opportunities and challenges for weed control and engineered resilience
3887Barrett, LGL, Mathieu; Kumaran, Nagalingam; Glassop, Donna; Raghu, S.; Gardiner, Donald M., Proceedings of the Royal Society B: Biological Sciences, 286:9. 2019-01-05 00:00:00.
Plant species, populations and communities are under threat from climate change, invasive pathogens, weeds and habitat fragmentation. Despite considerable research effort invested in genome engineering for crop improvement, the development of genetic tools for the management of wild plant populations has rarely been given detailed consideration. Gene drive systems that allow direct genetic management of plant populations via the spread of fitness-altering genetic modifications could be of great utility. However, despite the rapid development of synthetic tools and their enormous promise, little explicit consideration has been given to their application in plants and, to date, they remain untested. This article considers the potential utility of gene drives for the management of wild plant populations, and examines the factors that might influence the design, spread and efficacy of synthetic drives. To gain insight into optimal ways to design and deploy synthetic drive systems, we investigate the diversity of mechanisms underlying natural gene drives and their dynamics within plant populations and species. We also review potential approaches for engineering gene drives and discuss their potential application to plant genomes. We highlight the importance of considering the impact of plant life-history and genetic architecture on the dynamics of drive, investigate the potential for different types of resistance evolution, and touch on the ethical, regulatory and social challenges ahead.
Genetic manipulation of sex ratio in mammals: the Reaper comes for Mickey
3947Smanski, MJZ, David, EMBO reports, 20:e48577. 2019-01-05 00:00:00.
In most animals, sexual reproduction results in a 1:1 ratio of females to males. For several sectors of agriculture, for example, milk or egg production, only a single sex is needed. Biasing the sex ratio so that only offspring of the desired sex are produced has the potential to increase breeding efficiency. In this issue of EMBO Reports, Yosef et al [1] demonstrate a genetic approach to bias the sex ratio in mice by specifically disrupting essential genes in male embryos. Their approach is an important first step toward generating sex-ratio biasing applications for agriculture
Construction of an efficient genomic editing system with CRISPR/Cas9 in the vector mosquito Aedes albopictus
3926Liu, TY, W. Q.; Xie, Y. G.; Liu, P. W.; Xie, L. H.; Lin, F.; Li, C. Y.; Gu, J. B.; Wu, K.; Yan, G. Y.; Chen, X. G., Insect Science, 26:1045-1054. 2019-01-04 00:00:00.
Aedes (Stegomyia) albopictus, also known as the Asian tiger mosquito, is a mosquito which originated in Asia. In recent years, it has become increasingly rampant throughout the world. This mosquito can transmit several arboviruses, including dengue, Zika and chikungunya viruses, and is considered a public health threat. Despite the urgent need of genome engineering to analyze specific gene functions, progress in genetical manipulation of Ae. albopictus has been slow due to a lack of efficient methods and genetic markers. In the present study, we established targeted disruptions in two genes, kynurenine hydroxylase (kh) and dopachrome conversion enzyme (yellow), to analyze the feasibility of generating visible phenotypes with genome editing by the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) system in Ae. albopictus. Following Cas9 single guide RNA ribonucleoprotein injection into the posterior end of pre-blastoderm embryos, 30%-50% of fertile survivors produced alleles that failed to complement existing kh and yellow mutations. Complete eye and body pigmentation defects were readily observed in G1 pupae and adults, indicating successful generation of highly heritable mutations. We conclude that the CRISPR/Cas9-mediated gene editing system can be used in Ae. albopictus and that it can be adopted as an efficient tool for genome-scale analysis and biological study.
Sustainability as a framework for considering gene drive mice for invasive rodent eradication
3886Barnhill-Dilling, SKS, M.; Blondel, D. V.; Godwin, J., Sustainability, 11:1334. 2019-01-04 00:00:00.
Gene drives represent a dynamic and controversial set of technologies with applications that range from mosquito control to the conservation of biological diversity on islands. Currently, gene drives are being developed in mice that may one day serve as an important tool for reducing invasive rodent pests, a key threat to island biodiversity and economies. Gene drives in mice are still in development in laboratories, and wild release of modified mice is likely a distant reality. However, technological changes outpace the existing capacity of regulatory frameworks, and thus require integrated governance frameworks. We suggest sustainability-which gives equal consideration to the environment, economy, and society-as one framework for addressing complexity and uncertainty in the governance of emerging gene drive technologies for invasive species management. We explore the impacts of rodent gene drives on island environments, including potential conservation and restoration of island biodiversity. We outline considerations for rodent gene drives on island economies, including impacts on agricultural and tourism losses, and reductions in biosecurity costs. Finally, we address the social dimension as an essential space for deliberation that will be integral to evaluating the potential deployment of gene drive rodents on islands.
Targeting female reproduction in insects with biorational insecticides for pest management: a critical review with suggestions for future research
3946Smagghe, GZ, M.; Retnakaran, A., Current Opinion in Insect Science, 31:65-69. 2019-01-04 00:00:00.
Of the different approaches to pest control, use of juvenile hormone analogs (e.g. methoprene), molting hormone (20-hydroxyecdysone) analogs (e.g. tebufenozide) and chitin synthesis inhibitors (e.g. diflubenzuron) has dominated this field. Since they adversely interfere with the normal growth and development in one way or another, they have been collectively called as 'insect growth regulators' or IGRs. A lesser known fact is that they all have deleterious effects on reproduction as well as act as ovicides. The raison d'etre for this review is to summarize what we have learnt during the last 3-4 decades in the use of these IGRs, how they affect insect reproduction and how we can apply this knowledge to control pest insects. Finally, we present, information on the state of the art use of molecular technologies such as RNAi and CRISPR/Cas9 applications for pest management targeting insect reproduction.
Informed consent and community engagement in open field research: lessons for gene drive science
3945Singh, JA, BMC Medical Ethics, 20:54. 2019-01-03 00:00:00.
The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene drive constructs to reduce or suppress mosquito populations to levels that do not support disease transmission. Despite this prospect, social resistance to genetically modified organisms remains high. Gene drive open field research thus raises important questions regarding what is owed to those who may not consent to such research, or those could be affected by the proposed research, but whose consent is not solicited. The precise circumstances under which informed consent must be obtained, and from whom, requires careful consideration. Furthermore, appropriate engagement processes should be central to any introduction of genetically modified mosquitos in proposed target settings.
Next-generation CRISPR-based gene drive supports genetic editing with selective precision
3885Anonymous, International Sugar Journal, 121:411-412. 2019-01-03 00:00:00.
New CRISPR-based gene drives and broader active genetics technologies are revolutionizing the way scientists engineer the transfer of specific traits from one generation to another.
Two minutes to midnight-what international law can do about genome editing
3925Lee, TL, Asian Journal of Wto & International Health Law and Policy, 14:227-265. 2019-01-03 00:00:00.
With its ability to transform the ecosystem, gene drives, a powerful genome-editing technology, poses nuanced regulatory challenges. In particular, as gene drives can override the normal rule of inheritance, where the impacts of gene-drive modified organisms on the environment could be irreversible, leading to a permanent population change. Moreover, as these gene-drive modified organisms are designed to spread to large populations, they can also penetrate national and geographic borders, with global implications. Insofar as gene drive applications could be both potentially beneficial as well as hazardous to the world, this article seeks to explore ways in which international law could provide a useful platform to engage the relevant stakeholders in general, and encourage responsible science in specific.
Alternative strategies for mosquito-borne arbovirus control
3884Achee, NLG, J. P.; Vatandoost, H.; Seixas, G.; Pinto, J.; Ching-Ng, L.; Martins, A. J.; Juntarajumnong, W.; Corbel, V.; Gouagna, C.; David, J. P.; Logan, J. G.; Orsborne, J.; Marois, E.; Devine, G. J.; Vontas, J., PLOS Neglected Tropical Diseases, 13:e0006822. 2019-01-02 00:00:00.
Mosquito-borne virusessuch as Zika, chikungunya, dengue fever, and yellow fever, among othersare of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses. Methods and findings This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact. Conclusions As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission. Author summary International public health workers are challenged by the burden of arthropod-borne viral diseases, to include mosquito-borne arboviruses transmitted by Aedes aegypti and A. albopictus due in part to lack of sustainable vector control and insecticide resistance (IR), as well as the inability to scale up and sustain existing interventions for prevention of urban epidemics. As a consequence, there has been increasing interest to advance the development of alternative methods. This review provides a general overview of alternative vector-control strategies under development for the control of arbovirus mosquito vectors and highlights how each could offer innovative public health value. Considerations to regulations, acceptance, and sustainability are also provided.
Biocontrol in Australia: Can a carp herpesvirus (CyHV-3) deliver safe and effective ecological restoration?
3924Kopf, RKB, M.; Finlayson, C. M.; Hodges, K.; Humphries, P.; King, A.; Kingsford, R. T.; Marshall, J.; McGinness, H. M.; Thresher, R.; Vanderplasschen, A., Biological Invasions, 21:1857-1870. 2019-01-02 00:00:00.
The Australian Government is considering Cyprinid herpesvirus 3 (CyHV-3) for biocontrol of invasive common carp (Cyprinus carpio L.). We review the evidence-base for its potential ecological risks, benefits and effectiveness. Lower carp abundance may boost native fish biomass and improve water clarity, but there is little evidence available to suggest that the virus, alone or used in combination with other methods, can deliver effective or safe biocontrol. Further, the virus may already be present in Australia. Overseas, the virus has caused sporadic and localized mortalities of carp in lakes and rivers, but has generally had no long-term measurable effect on wild carp or native fish populations. The temperature range of disease (18-28 degrees C), unknown co-factors causing outbreaks, and predictable re-colonization and recruitment boom of immune and virus-resistant carp, following a biocontrol release, remain formidable and unmitigated barriers to success. CyHV-3 infection trials on Australian biota have unexplained high mortality rates of recreationally-important and threatened fishes, and the role of asymptomatic carriers remains uncertain. Finally, Australia has national and international obligations to ensure that there are no perverse outcomes from biocontrol actions. Despite political pressure, there is no environmental justification to rush the release of this virus. To achieve the Government goals of restoring native biodiversity we advocate that key uncertainties, risks and efficacy barriers first need to be addressed. It is only then that viral biocontrol could be considered a viable tool to complement broader ecological restoration strategies for Australia's waterways.
Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species
3904Courtier-Orgogozo, VD, Antoine; Gouyon, Pierre-Henri; Boëte, Christophe, bioRxiv, 776609:27. 2019-01-02 00:00:00.
The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct withhyb = probability of hybridization between the target species and a non-target speciestransf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a non-target species (with no hybridization)express = probability that the Cas9 and guide RNA genes are expressedcut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new hostflank = probability that the gene drive cassette inserts at the cut siteimmune = probability that the immune system does not reject Cas9-expressing cellsnonextinct = probability of invasion of the drive within the population We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.CRISPRClustered Regularly Interspaced Short Palindromic RepeatsDRAQUEDrive Risk Assessment Quantitative EstimateHGThorizontal gene transferHTThorizontal transfer of transposable elementTEtransposable element
Two-By-One model of cytoplasmic incompatibility: Synthetic recapitulation by transgenic expression of cifA and cifB in Drosophila
3944Shropshire, JDB, S. R., PLOS Genetics, 15:e1008221. 2019-01-02 00:00:00.
Wolbachia are maternally inherited bacteria that infect arthropod species worldwide and are deployed in vector control to curb arboviral spread using cytoplasmic incompatibility (CI). CI kills embryos when an infected male mates with an uninfected female, but the lethality is rescued if the female and her embryos are likewise infected. Two phage WO genes, cifA(wMel) and cifB(wMel) from the wMel Wolbachia deployed in vector control, transgenically recapitulate variably penetrant CI, and one of the same genes, cifA(wMel), rescues wild type CI. The proposed Two-by-One genetic model predicts that CI and rescue can be recapitulated by transgenic expression alone and that dual cifA(wMel) and cifB(wMel) expression can recapitulate strong CI. Here, we use hatch rate and gene expression analyses in transgenic Drosophila melanogaster to demonstrate that CI and rescue can be synthetically recapitulated in full, and strong, transgenic CI comparable to wild type CI is achievable. These data explicitly validate the Two-by-One model in wMel-infected D. melanogaster, establish a robust system for transgenic studies of CI in a model system, and represent the first case of completely engineering male and female animal reproduction to depend upon bacteriophage gene products. Author summary Releases of Wolbachia-infected mosquitos are underway worldwide because Wolbachia block replication of Zika and Dengue viruses and spread themselves maternally through arthropod populations via cytoplasmic incompatibility (CI). The CI drive system depends on a Wolbachia-induced sperm modification that results in embryonic lethality when an infected male mates with an uninfected female, but this lethality is rescued when the female and her embryos are likewise infected. We recently reported that the phage WO genes, cifA and cifB, cause the sperm modification and cifA rescues the embryonic lethality caused by the wMel Wolbachia strain deployed in vector control. These reports motivated proposal of the Two-by-One model of CI whereby two genes cause lethality and one gene rescues it. Here we provide unequivocal support for the model in the Wolbachia strain used in vector control via synthetic methods that recapitulate CI and rescue in the absence of a Wolbachia infections. Our results reveal the set of phage WO genes responsible for this powerful genetic drive system, act as a proof-of-concept that these genes alone can induce gene drive like crossing patterns, and establish methodologies and hypotheses for future studies of CI in Drosophila. We discuss the implications of the Two-by-One model towards functional mechanisms of CI, the emergence of incompatibility between Wolbachia strains, vector control applications, and CI gene nomenclature.
An introduction to the proceedings of the environmental release of engineered pests: Building an international governance framewor
5646Brown, Z. S., L. Carter and F. Gould, BMC Proceedings, 12:10. 2018-12-17 17:44:54.
In October 2016, a two-day meeting of 65 academic, government and industry professionals was held at North Carolina State University for early-stage discussions about the international governance of gene drives: potentially powerful new technologies that can be used for the control of pests, invasive species and disease vectors. Presenters at the meeting prepared seven manuscripts elaborating on the ideas raised. This BMC Proceedings issue presents the collection of these peer-reviewed manuscripts.
Towards inclusive social appraisal: risk, participation and democracy in governance of synthetic biology
5642Stirling, A., K. R. Hayes and J. Delborne, BMC Proceedings, 12:15. 2018-12-17 17:05:25.
Frameworks that govern the development and application of novel products, such as the products of synthetic biology, should involve all those who are interested or potentially affected by the products. The governance arrangements for novel products should also provide a democratic mechanism that allows affected parties to express their opinions on the direction that innovation does or does not take. In this paper we examine rationales, obstacles and opportunities for public participation in governance of novel synthetic biology products. Our analysis addresses issues such as uncertainties, the considering of alternative innovations, and broader social and environmental implications. The crucial issues in play go beyond safety alone, to include contending social values around diverse notions of benefit and harm. The paper highlights the need for more inclusive social appraisal mechanisms to inform governance of Synthetic Biology and alternative products, and discusses a few practical methods to help achieve this goal.
Public engagement pathways for emerging GM insect technologies
5640Burgess, M. M., J. D. Mumford and J. V. Lavery, BMC Proceedings, 12(Suppl 8):12. 2018-12-17 17:02:52.
Policy and management related to the release of organisms generated by emerging biotechnologies for pest management should be informed through public engagement. Regulatory decisions can be conceptually distinguished into the development of frameworks, the assessment of the release of a specific modified organism, and implementation decisions such as location and timing. Although these decisions are often intertwined in practice, the negotiation takes place at different stages of technology development and suggests different roles for public engagement. Some approaches to public engagement are more appropriate for different purposes and situations, and it is not always obvious how to go about matching the approach to the purpose. In addition to the diverse technologies involved in generating modified organisms, there are diverse publics with particular interests and different kinds of knowledge. Institutional interests range from commercial development to public regulation and future uptake. Contextual features, such as agency mandates, may limit or structure the extent and approach to public engagement. Different convening groups (government agencies, public interest groups, academics, businesses) and the kind of decision that is being considered determine what kind of input is needed and how the engaging groups will be constituted. This paper considers how the context of the release of genetically modified insects for pest control requires expanding approaches to the design of the public engagement.
GM insect pests under the Brazilian regulatory framework: development and perspectives
5638Andrade, P. P., M. A. da Silva Ferreira, M. S. Muniz and A. de Casto Lira-Neto, BMC Proceedings, 12:15. 2018-12-17 17:00:23.
The emergence of new technologies for genetic modification has broadened the range of possible new products. The regulations of many countries that could benefit from these new products may not be prepared to assess risks and enable science-based decision-making. This is especially acute in the case of genetically modified insects with potential use in public health and agriculture. Modifications of the regulatory framework, sometimes necessary to allow a proper risk assessment of products from new technologies, are strongly influenced by political decisions derived from the balance of power and interest among stakeholders. This article discusses the genesis of the Brazilian regulatory framework, its applicability for the risk assessment of genetically modified insects and the scenarios that have shaped the two biosafety laws that established the basis for the use of modern biotechnology in the country. It is concluded that, for the adoption of the new technologies, it is important to carefully navigate the political tensions by seeking the engagement and empowerment of stakeholders supporting science-based decision-making in order to gather the necessary support for adoption of risk assessment as the basis for final decisions, allowing the use of new technologies.
Regulation of emerging gene technologies in India
5636Ahuja, V., BMC Proceedings, 12:14. 2018-12-17 16:57:35.
In India, genetically modified organisms (GMOs) and the products thereof are regulated under the “Rules for the manufacture, use, import, export & storage of hazardous microorganisms, genetically engineered organisms or cells, 1989” (referred to as Rules, 1989) notified under the Environment (Protection) Act, 1986. These Rules are implemented by the Ministry of Environment, Forest and Climate Change, Department of Biotechnology and State Governments though six competent authorities. The Rules, 1989 are supported by series of guidelines on contained research, biologics, confined field trials, food safety assessment, environmental risk assessment etc.
Population Engineering | Gene Drive by CRISPR-CAS9
5488SciToons, 2018-12-10 18:19:26.
The CRISPR-CAS9 genome editing technology is opening up previously inconceivable possibilities for the manipulation of organisms. Our ethical discussion appears to be far behind the pace of technological development. In this new SciToons video, we address how CRISPR-CAS9 can be used to change entire species using the concept of Gene Drive.
CRISPR Gene Drive (Complete guide 2019)
5507Every Cell A Universe, 2018-11-18 18:59:09.
Crispr gene drive - malaria cure and a new way to look at conservation.
Yes we can! Exciting progress and prospects for controlling invasives on islands and beyond
7964D. Simberloff, B. Keitt, D. Will, N. Holmes, E. Pickett and P. Genovesi, Western North American Naturalist, 78:942-958. 2018-10-22 14:34:34.
Eradication and maintenance management of island invasive species have long histories, and incremental improvements of existing technologies plus occasional novel approaches have led to more challenging targets and increased success rates in certain categories. Many nonnative mammals have been eradicated from islands, as have several nonnative birds, insects, and plants. Hundreds of rat populations have been eliminated, with a success rate over 80%, and islands over 10,000 ha are now feasible targets. Mouse eradication has proven more challenging, but aerial broadcast of anticoagulant toxins has led to increased success. Carnivore eradication-especially of feral housecats and foxes-has been frequently attempted with a recent success rate over 90%. Eradication of herbivores-primarily goats, rabbits, wild boar, and boar/pig hybrids-has been attempted almost 200 times, with a success rate over 90%. Trends in mammal eradication include more frequent attempts and higher success rates on larger islands and inhabited islands, as well as attempts targeting multiple invasive species. Documented conservation gains from island mammal eradications are numerous. For insects, about two-thirds of some 50 island attempts have succeeded, and most targeted agricultural pests. No summary statistics exist on island plant eradications, but several small infestations have been eradicated. Several insect and plant island invaders have been maintained at low densities by biological control, and plants have been controlled short of eradication by herbicides, often combined with physical or mechanical means. Failures in both eradication and maintenance management on islands often result from insufficient long-term commitment of resources. Excitement and controversy abound over the prospect that new techniques relying on molecular genetic tools-especially RNA-guided gene drives-may permit eradication or maintenance management of nonnative invaders in situations that have previously appeared extremely difficult or infeasible. Island populations of invertebrates, small mammals, and some plants are particularly propitious targets.
Multiple loci of small effect confer wide variability in efficiency and resistance rate of CRISPR gene drive
11267J. Champer, Z. Wen, A. Luthra, R. Reeves, J. Chung, C. Liu, Y. L. Lee, J. Liu, E. Yang, P. W. Messer and A. G. Clark, bioRxiv, 447615. 2018-10-19 19:06:27.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation post-fertilization in the early embryo ranged from 7% to 79% among lines and averaged 42±18%. We performed a Genome-Wide Association Study (GWAS) using our results in the DGRP lines and found that the resistance and conversion rates were polygenic, with several genetic polymorphisms showing relatively weak association. RNAi knockdown of several of these genes confirmed their effect, but their small effect sizes implies that their manipulation will yield only modest improvements to the efficacy of gene drives.
A Call to Protect Food Systems from Genetic Extinction Technology
12040Global Food and Agriculture Movement, etc Group, 2018-10-16 20:31:12.
Gene drives threaten natural systems. If released experimentally into the environment they may spread engineered genes uncontrollably through wild and domesticated species. This could alter ecological systems and food webs, harm biodiversity and eradicate beneficial organisms such as pollinators. Gene drives could disrupt lands, waters, food and fiber economies and harm Indigenous and peasant agroecological practices and cultures.
Just Say No to Agricultural Gene Drives
4722Bassey-Orovwuje, M., Project Syndicate, 2018-10-16 00:00:00.
By forcing laboratory-made genes on an entire population or species, cutting-edge gene-drive technologies have the power to transform entire ecosystems in one fell swoop. But where leading industrial agriculture firms see dollar signs, farmers in the regions where gene drives could be unleashed see a mortal threat to their livelihoods.
Gene drive used to turn all female mosquitos sterile
4589Timmer, J, ARS Technica, 2018-09-27 00:00:00.
We've known for a long time that we can limit malaria infections by controlling the mosquitos that transmit them. But that knowledge hasn't translated into control efforts that have always been completely successful. Many of the approaches we've used to control mosquitos have caused environmental problems, and mosquito populations are large enough that they have evolved resistance to many of our pesticides.; ; That made the development of what are called "gene drive" constructs exciting (if a bit scary). They have the potential to rapidly spread genes throughout a population—including a mosquito population. But the prospect of a modern genetic control of mosquito populations has run up against the very old problem of evolution, as the gene drives often stall due to genetic changes that allow mosquito populations to escape their impact.
Invasion Success and Management Strategies for Social Vespula Wasps
13740P. J. Lester and J. R. Beggs, Annual Review of Entomology, 64:51-71. 2018-09-26 19:38:03.
Three species of Vespula have become invasive in Australia, Hawai'i, New Zealand, and North and South America and continue to spread. Economically, their main negative effect is associated with pollination and the apicultural industry. Climate change is likely to exacerbate their impacts in many regions. Although investigated extensively, no effective biological control agents have yet been found. Emerging technologies such as gene drives are under consideration.
Malaria mosquitoes wiped out in lab trials of gene drive testing
4568Kelland, K, The Wire, 2018-09-26 00:00:00.
London: Scientists have succeeded in wiping out a population of caged mosquitoes in laboratory experiments using a type of genetic engineering known as a gene drive, which spread a modification blocking female reproduction.; ; The researchers, whose work was published on Monday in the journal Nature Biotechnology, managed to eliminate the population in less than 11 generations, suggesting the technique could in future be used to control the spread of malaria, a parasitic disease carried by Anopheles gambiae mosquitoes.
Gene drives could wipe out mosquitoes
5513New Scientist, 2018-09-25 19:10:14.
This is a short video describing how gene drive is being considered for controlling malaria transmitting mosquitoes in Africa as part of ongoing malaria eradication efforts.
Gene drives breakthrough needs urgent restraint
4586Steinbrecher, R, GMWatch, 2018-09-24 00:00:00.
Gene drive researchers associated with Target Malaria and funded by US DARPA, the GATES Foundation and the UK BBSRC have just managed to crash a population of caged mosquitoes after 7-11 generations.(1); ; This is a first, and it has brought this technology beyond the proof of principle. However, in their effort to avoid any resistance to the gene drive, they have focused on a highly stable, ‘conserved’ and vital gene that is found in many species, especially closely related mosquito species. This could enable the gene drive to eliminate populations of multiple non-target species, with very serious implications indeed for biodiversity and ecosystems.; ; We begin by explaining something about gene drives before focusing on what is different about this latest research just published by Kyrou et al. 2018 in Nature Biotechnology.
Here’s the Plan to End Malaria With Crispr-Edited Mosquitoes
4571Molteni, M, Wired, 2018-09-24 00:00:00.
In 2003, scientists at London’s Imperial College hatched a somewhat out-there idea. They wanted to deal with the increasingly pesticide-resistant mosquitoes that were killing half a million people a year by spreading malaria in sub-Saharan Africa. What biologists Austin Burt and Andrea Crisanti proposed was nothing short of hacking the laws of heredity.; ; By planting a deadly gene in mosquito DNA, and engineering it such that the modification would spread through each generation faster than nature intended, they figured they could completely crash a population with just a few Trojan skeeters. This concept of a “gene drive” was decades-old, but no one had successfully concocted one in a lab, let alone applied it to a global public health scourge.
Pest demography critically determines the viability of synthetic gene drives for population control
11505K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross, Mathematical Biosciences, 305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.
A sustainable synthetic biology approach for the control of the invasive golden mussel (Limnoperna fortunei)
19204M. F. Rebelo, L. F. Afonso, J. A. Americo, L. da Silva, J. L. B. Neto, F. Dondero and Q. Zhang, PeerJ Preprints, 6:e27164v3. 2018-09-12 14:52:07.
The recent development of the CRISPR-Cas9-based gene drive has created the conditions to seriously consider this technology to solve one of the major environmental challenges in biodiversity conservation i.e. the control of invasive species. There is no efficient control method for golden mussel infestation available so far. Here we discuss the technical and economic feasibility of using a synthetic biology based approach to fight and control the invasive mussel Limnoperna fortunei in South American rivers and reservoirs.
For the first time, researchers will release genetically engineered mosquitoes in Africa
11444Ike Swetitz, STAT, 2018-09-05 18:02:01.
The government of Burkina Faso granted scientists permission to release genetically engineered mosquitoes anytime this year or next, researchers announced Wednesday. It’s a key step in the broader efforts to use bioengineering to eliminate malaria in the region.
Ethics of sculpting evolution
7338K. Esvelt, PopTech, 2018-09-04 21:34:19.
How might supervillains take over the world, and what can we do about it? Kevin Esvelt, the first to identify the potential for CRISPR “gene drive” systems to alter entire populations of organisms, is calling for a new scientific method that is both open and gives beneficiaries a say in the process.
Existing rules cover gene-drive usage
4728Strassheim, S.S., W., Nature, 2018-07-18 00:00:00.
Gene Drives
6636SciLine, SciLine, 2018-04-25 20:09:28.
For many years now, scientists have been able to alter genes inside microbial, plant, and animal cells to change organisms’ traits, creating, for example, plants that produce their own protective insecticides and fish that grow to maturity almost twice as fast as normal. But while it has become practically routine for scientists to genetically alter individual organisms, a new set of advances promises something much more ambitious: the ability to propagate new genetic traits* into entire populations over just a few generations. Rapid, population-wide dissemination of new traits is challenging because in most sexually reproducing species, only half of an individual’s offspring will inherit any given version of a gene.
RealSciLine | Gene Drives Media Briefing
6513Rick Weiss, RealSciLine, 2018-04-25 16:07:20.
Gene drives represent a new take on genetic engineering offering previously impossible means of fighting disease-spreading insects and invasive species but also raising the specter of ecological disruption. This briefing reviews the current status of gene-drive technology, applications under consideration, and related ethical, legal, and regulatory issues.
The ethical implications of population suppression and the irreversibility of gene drives
14167J. Kim, International Journal of Life Sciences Research, 2018-04-01 14:11:25.
This paper aims to examine the current situation by presenting important ethical arguments that include Chardin’s principle of irreversibility and Weiss’ beliefs on intergenerational equity, ideals upheld by the United Nations
Transgenic Mosquitoes – Fact or Fiction?
5907Wilke, A. B. B., J. C. Beier and G. Benelli, Trends in Parasitology, 34:456-465. 2018-03-08 16:14:34.
echnologies for controlling mosquito vectors based on genetic manipulation and the release of genetically modified mosquitoes (GMMs) are gaining ground. However, concrete epidemiological evidence of their effectiveness, sustainability, and impact on the environment and nontarget species is lacking; no reliable ecological evidence on the potential interactions among GMMs, target populations, and other mosquito species populations exists; and no GMM technology has yet been approved by the WHO Vector Control Advisory Group. Our opinion is that, although GMMs may be considered a promising control tool, more studies are needed to assess their true effectiveness, risks, and benefits. Overall, several lines of evidence must be provided before GMM-based control strategies can be used under the integrated vector management framework.
Population modification of Anopheline species to control malaria transmission
6694R. Carballar-Lejarazú and A. A. James, Pathogens and Global Health, 111:424-435. 2018-02-01 17:58:10.
Vector control strategies based on population modification of Anopheline mosquitoes may have a significant role in the malaria eradication agenda. They could consolidate elimination gains by providing barriers to the reintroduction of parasites and competent vectors, and allow resources to be allocated to new control sites while maintaining treated areas free of malaria. Synthetic biological approaches are being used to generate transgenic mosquitoes for population modification. Proofs-of-principle exist for mosquito transgenesis, the construction of anti-parasite effector genes and gene-drive systems for rapidly introgressing beneficial genes into wild populations. Key challenges now are to develop field-ready strains of mosquitoes that incorporate features that maximize safety and efficacy, and specify pathways from discovery to development. We propose three pathways and a framework for target product profiles that maximize safety and efficacy while meeting the demands of the complexity of malaria transmission, and the regulatory and social diversity of potential end-users and stakeholders.
Gene drives and the management of agricultural pests
13810R. F. Medina, Journal of Responsible Innovation, 5:S255-S262. 2018-01-24 16:01:13.
Like all pest control strategies, gene drives are not hazard-free. Ecological risk assessment of gene drives designed to control agricultural pests should be conducted before their deployment. The present commentary provides some thoughts on some of the issues one should consider when contemplating using gene drives in the management of agricultural pests.
Summary
13808Committee on Gene Drive Research in Non-Human Organisms: Recommendations for Responsible, Journal of Responsible Innovation, 5:S243-S254. 2018-01-24 15:58:19.
Scientists have studied gene drives for more than 50 years. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussion of the potential applications and implications of gene drive technologies.
Anomaly handling and the politics of gene drives
13806S. W. Evans and M. J. Palmer, Journal of Responsible Innovation, 5:S223-S242. 2018-01-24 15:56:09.
Decisions about the development and use of gene drives are framing broader debates about the need for fundamental changes to biotechnology regulatory systems. We summarize this debate and describe how gene drives are being constructed as potential anomalies within the regulatory landscape.
Regulating animals with gene drive systems: lessons from the regulatory assessment of a genetically engineered mosquito
13804Z. Meghani and J. Kuzma, Journal of Responsible Innovation, 5:S203-S222. 2018-01-24 15:52:57.
In this paper, we consider the question of whether the United States Food and Drug Administration is prepared to effectively regulate insects and other animals with gene drives. Given the profound impact that gene drives could have on species and ecosystems, their use is a highly contentious issue. The rigorous regulation of insects and other animals with gene drive systems is crucial.
Developing gene drive technologies to eradicate invasive rodents from islands
13798C. M. Leitschuh, D. Kanavy, G. A. Backus, R. X. Valdez, M. Serr, E. A. Pitts, D. Threadgill and J. Godwin, Journal of Responsible Innovation, 5:S121-S138. 2018-01-24 15:45:57.
Gene drive methods of rodent eradication offer an alternative to killing that has the potential to be more species-specific, more humane, and more biologically safe for use around humans. Implementing this technology would involve releasing laboratory-developed engineered mice into wild populations. Some areas for further research include assessing the ecological effects of releasing engineered mice, the potential risks for the accidental or deliberate release of genetically modified organisms into mainland mouse populations, and the social, ethical, and regulatory acceptability of the technology.
Agricultural production: assessment of the potential use of Cas9-mediated gene drive systems for agricultural pest control
13796M. J. Scott, F. Gould, M. Lorenzen, N. Grubbs, O. Edwards and D. O’Brochta, Journal of Responsible Innovation, 5:S98-S120. 2018-01-24 15:43:20.
To highlight how gene drives could be useful for control of agricultural insect pests, we selected species that are pests of animals (New World screwworm), plants (spotted wing Drosophila, diamondback moth, Bemisia tabaci whitefly), or stored grains (red flour beetle). We provide examples of gene drives that target specific genes including female-essential genes. Further, we discuss issues related to containment in the laboratory and eventual field testing of strains harboring a Cas9-mediated gene drive system.
A roadmap for gene drives: using institutional analysis and development to frame research needs and governance in a systems context
13790J. Kuzma, F. Gould, Z. Brown, J. Collins, J. Delborne, E. Frow, K. Esvelt, D. Guston, C. Leitschuh, K. Oye and S. Stauffer, Journal of Responsible Innovation, 5:S13-S39. 2018-01-24 15:34:37.
This paper reports on a workshop held in February 2016 to explore the complex intersection of political, economic, ethical, and ecological risk issues associated with gene drives. Workshop participants were encouraged to use systems thinking and mapping to describe the connections among social, policy, economic, and ecological variables as they intersect within governance systems. In this paper, we analyze the workshop transcripts and maps using the Institutional Analysis and Development (IAD) framework to categorize variables associated with gene drive governance and account for the complexities of socio-ecological systems.
Mapping research and governance needs for gene drives
13788J. Delborne, J. Kuzma, F. Gould, E. Frow, C. Leitschuh and J. Sudweeks, Journal of Responsible Innovation, 5:S4-S12. 2018-01-24 15:28:09.
This special issue represents both deep and broad thinking about gene drives. The papers were first drafted nearly two years ago, and since then have been reviewed and revised to flesh out key arguments and take account of ongoing developments in the field. This field has moved very fast indeed! Technical research publications have increased in number; NASEM released a major report in June 2016; and workshops have proliferated.
Gene drives and the expanding horizon of governance
13786E. Fisher, Journal of Responsible Innovation, 5:S1-S3. 2018-01-24 15:23:59.
Like other areas of emerging science and technology that trigger prolonged public debate over their transformative prospects, gene drives simultaneously generate prospects for new knowledge, hoped-for benefits, and formidable concerns. Their ability to bias inheritance of and in theory spread a genetic trait throughout an entire population of organisms—even to the point of extinction—is driving home the need for their responsible governance. Significantly, it is also driving home the need to develop capacities for such governance.
Gene drive to reduce malaria transmission in sub-Saharan Africa
3963Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.
Safe Driving: CRISPR and the Gene Drive Landscape
4003Nolan, T, CRISPR Journal, 1:16-18. 2018-01-21 00:00:00.
A New Study Highlights Issues About the Capability to Limit Gene Drives in the Field to a Target Population
Current CRISPR gene drive systems are likely to be highly invasive in wild populations
4002Noble, CA, Ben; Church, George M.; Esvelt, Kevin M.; Nowak, Martin A., eLife, 7:e33423. 2018-01-20 00:00:00.
Recent reports have suggested that self-propagating CRISPR-based gene drive systems are unlikely to efficiently invade wild populations due to drive-resistant alleles that prevent cutting. Here we develop mathematical models based on existing empirical data to explicitly test this assumption for population alteration drives. Our models show that although resistance prevents spread to fixation in large populations, even the least effective drive systems reported to date are likely to be highly invasive. Releasing a small number of organisms will often cause invasion of the local population, followed by invasion of additional populations connected by very low rates of gene flow. Hence, initiating contained field trials as tentatively endorsed by the National Academies report on gene drive could potentially result in unintended spread to additional populations. Our mathematical results suggest that self-propagating gene drive is best suited to applications such as malaria prevention that seek to affect all wild populations of the target species.
Means and ends of effective global risk assessments for genetic pest management
4022Turner, GB, Camilla; Roda, Lucia, BMC Proceedings, 12:13. 2018-01-20 00:00:00.
The development and use of genetic technologies is regulated by countries according to their national laws and governance structures. Legal frameworks require comprehensive technical evidence to be submitted by an applicant on the biology of the organism, its safety to human, animal health and the environment in which it will be released. Some countries also require information on socio-economic and trade impacts. One of the key elements that assists decision-making under those legal frameworks is the use of risk assessments. The risk assessment paradigm of problem formulation based on risk hypothesis, and the assessment of plausible scientific pathways leading to potential environmental and human harms being realised, has been used widely to assess potential risks of genetic technologies to human health and the environment, from crops to mosquitoes. This paper uses the case study of a genetically modified self-limiting olive fly (Bactrocera oleae) for a first deliberate release in Spain to examine the regulatory processes and stakeholders involved in the assessment of risk. It is anticipated that existing risk assessment frameworks are equally applicable to gene drive technologies that may spread and persist in the environment and cross-national borders, but it is the governance structures surrounding the involvement of civil society in regulatory processes that must be administered in a more transparent and defined manner.
Pathway to deployment of gene drive mosquitoes as a potential biocontrol tool for elimination of malaria in sub-Saharan Africa: Recommendations of a scientific working group
3982James, SC, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A.; Tountas, Karen H.; Touré, American Journal of Tropical Medicine and Hygiene, 98:1-49. 2018-01-20 00:00:00.
Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.
Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii
3962Buchman, AM, John M.; Ostrovski, Dennis; Yang, Ting; Akbari, Omar S., Proceedings of the National Academy of Sciences of the United States of America, 115:4725-4730. 2018-01-20 00:00:00.
Here we describe a fully functional gene drive system constructed in a major worldwide crop pest, Drosophila suzukii. This system is composed of a synthetic Medea drive with a maternal miRNA “toxin” and a zygotic “antidote,” and we demonstrate that it can bias inheritance with 100% efficiency and can persist in a population given high release frequencies. We discuss how such a system may be used to suppress D. suzukii populations or render them harmless to target crops.Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii. We demonstrate that this drive system, based on an engineered maternal “toxin” coupled with a linked embryonic “antidote,” is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest.
Can We Engineer Social Ecosystems?
5473Kevin Esvelt, TEDxCambridgeSalon, 2018-01-19 17:11:31.
Kevin Esvelt is director of the Sculpting Evolution group, which invents new ways to study and influence the evolution of ecosystems. By carefully developing and testing these methods with openness and humility, the group seeks to address difficult ecological problems for the benefit of humanity and the natural world. Prior to joining the MIT Media Lab, Esvelt wove many different areas of science into novel approaches to ecological engineering.
Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila
3961Buchman, ABI, Tobin; Marshall, John M.; Akbari, Omar S.; Hay, Bruce A., ACS Synthetic Biology, 7:1359-1370. 2018-01-19 00:00:00.
Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions using gene drive provides a self-perpetuating method of disease prevention. Mechanisms that require the gene drive element and linked cargo to exceed a high threshold frequency in order for spread to occur are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold frequency required for drive. Reciprocal chromosome translocations were proposed as a tool for bringing about high threshold population replacement in 1940 and 1968. However, translocations able to achieve this goal have only been reported once, in the spider mite Tetranychus urticae, a haplo-diploid species in which there is strong selection in haploid males for fit homozygotes. We report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. These strains drive high threshold population replacement in laboratory populations. While it remains to be shown that engineered translocations can bring about population replacement in wild populations, these observations suggest that further exploration of engineered translocations as a tool for controlled population replacement is warranted.
Population seasonality and release timing significantly affect the probability of establishment for small releases of gene drive mosquitoes
4001Nikolov, MO, A. L.; Beaghton, A. K.; Beaghton, P. J.; Wenger, E. A.; Burt, A.; Welkhoff, P. A., American Journal of Tropical Medicine and Hygiene, 99:367-367. 2018-01-19 00:00:00.
Highly efficient CRISPR/Cas9 gene-drive systems have recently been developed, targeting reproductive-capacity and malaria-competency loci of malaria transmitting vector species, such as An. gambiae. The resulting drive systems aim to either suppress the local wild-type population or alter its genome, conveying desirable phenotypes such as P. falciparum refractoriness. The potential for sustained spread of gene drive constructs as proposed for malaria and a variety of other applications (pest control, tick borne diseases, dengue) has raised concerns for unintentional or unauthorized organism release outside approved and strictly-regulated trial sites. Previous analyses posit that as few as one or two gene drive organisms carrying efficient gene drive cassettes may establish a permanent (sub)population of genetically-modified (GM) mosquitoes with probability >50%. While these results are broad and cautionary, we show that seasonality is a fundamental environmental characteristic to consider when modeling decision variables. For the first time, we investigate the impact of gene-drive release timing and numbers on the establishment probability of GM vectors in the context of realistic seasonal population variation. We model a male sex bias, driving-Y population suppression gene drive, targeting An. gambiae, since these are among the first field trials candidate constructs. We analyze gene-drive establishment in geographies of different seasonality and spatial vector population features. We show that releasing a small number of gene-drive mosquitoes over the few weeks in the beginning of the wet season facilitates population founder effects and high establishment probability: between 60% - 80% for releases of as few as one or two mosquitoes. However, releasing genedrive mosquitoes outside this time results in much lower establishment probability, typically <20%. Our findings address crucial ethical and environmental concerns, which may guide whether, how, and where to set up gene-drive trials.
Developing standard operating procedures for gene drive research in disease vector mosquitoes
15680Z. N. Adelman, D. Pledger and K. M. Myles, Pathogens and Global Health, 111:436-447. 2018-01-18 14:41:42.
Here we discuss information to be considered by principal investigators, biosafety officers, and institutional biosafety committees as they work together to develop SOPs for experiments involving gene drive in arthropods, and describe various courses of action that can be used to maintain the effectiveness of SOPs through evaluation and revision. The information provided herein will be especially useful to investigators and regulatory personnel who may lack extensive experience working with arthropods under containment conditions.
Engineered integrative and conjugative elements for efficient and inducible DNA transfer to undomesticated bacteria
3960Brophy, JANT, Alexander J.; Adams, Bryn L.; Renberg, Rebecca L.; Stratis-Cullum, Dimitra N.; Grossman, Alan D.; Voigt, Christopher A., Nature Microbiology, 3:1043-1053. 2018-01-18 00:00:00.
Engineering microorganisms to promote human or plant health will require manipulation of robust bacteria that are capable of surviving in harsh, competitive environments. Genetic engineering of undomesticated bacteria can be limited by an inability to transfer DNA into the cell. Here we developed an approach based on the integrative and conjugative element from Bacillus subtilis (ICEBs1) to overcome this problem. A donor strain (XPORT) was built to transfer miniaturized integrative and conjugative elements (mini-ICEBs1) to undomesticated bacteria. The strain was engineered to enable inducible control over conjugation, to integrate delivered DNA into the chromosome of the recipient, to restrict spread of heterologous DNA through separation of the type IV secretion system from the transferred DNA, and to enable simple isolation of engineered bacteria through a d-alanine auxotrophy. Efficient DNA transfer (10–1 to 10–7 conjugation events per donor) is demonstrated using 35 Gram-positive strains isolated from humans (skin and gut) and soil. Mini-ICEBs1 was used to rapidly characterize the performance of an isopropyl-?-d-thiogalactoside (IPTG)-inducible reporter across dozens of strains and to transfer nitrogen fixation to four Bacillus species. Finally, XPORT was introduced to soil to demonstrate DNA transfer under non-ideal conditions.
Evaluating active genetic options for the control of Sea Lampreys (Petromyzon marinus) in the Laurentian Great Lakes
4020Thresher, REJ, Michael; Drake, D. Andrew, Canadian Journal of Fisheries and Aquatic Sciences, 76:1186-1202. 2018-01-18 00:00:00.
For more than two decades the Great Lakes Fishery Commission has sought tactics to complement, and potentially replace, the use of barriers and lampricides to control Sea Lamprey in the Great Lakes, but thus far without success. This paper examines the potential of modern genetic technology to suppress these invasive populations. We identified six recombinant options that appeared to be moderately to highly feasible, most of which were judged by an expert panel as extremely low or low risk, and for which R&D was broadly supported by stakeholders. The two options judged to overall best combine high efficacy and low risks were a Mendelian “sex ratio drive” and genetically modifying a prey species as to kill or sterilize Sea Lamprey that fed on it. Core issues regarding use of genetic biocontrol in the Great Lakes include technical problems associated with maintaining a Sea Lamprey brood line, information gaps for most options, the extent of broader public support, and the extent and nature of national and international consultation required in making decisions about control options.
Gene drive systems: Do they have a place in agricultural weed management?
4000Neve, P, Pest Management Science, 74:2672-2679. 2018-01-18 00:00:00.
There is a pressing need for novel control techniques in agricultural weed management. Direct genetic control of agricultural pests encompasses a range of techniques to introduce and spread novel, fitness-reducing genetic modifications through pest populations. Recently, the development of CRISPR-Cas9 gene editing has brought these approaches into sharper focus. Proof of concept for CRISPR-Cas9 based gene drives has been demonstrated for control of disease-vectoring insects. This article considers whether and how gene drives may be applied in agricultural weed management, focusing on CRISPR-Cas9 based systems. Population suppression drives might be employed to introduce and proliferate deleterious mutations that directly impact fitness and weediness, whereas population sensitizing drives would seek to edit weed genomes so that populations are rendered more sensitive to subsequent management interventions. Technical challenges relating to plant transformation and gene editing in planta are considered, and the implementation of gene drives for timely and sustainable weed management is reviewed in the light of weed population biology. The technical, biological, practical and regulatory challenges remain significant. Modelling-based studies can inform how and if gene drives could be employed in weed populations. These studies are an essential first step towards determining the utility of gene drives for weed management. This article is protected by copyright. All rights reserved.
Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms
3980Hayes, KRH, G. R.; Dana, G. V.; Foster, S. D.; Ford, J. H.; Thresher, R.; Ickowicz, A.; Peel, D.; Tizard, M.; De Barro, P.; Strive, T.; Dambacher, J. M., Journal of Responsible Innovation, 5:S139-S158. 2018-01-18 00:00:00.
Synthetic gene drives could provide new solutions to a range of old problems such as controlling vector-borne diseases, agricultural pests and invasive species. In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. We discuss the strengths and weaknesses of checklists and structured hazard analysis techniques, identify methods to help meet some of the challenges of detecting adverse ecological outcomes in experiments and confined field trials, and discuss ways to improve the efficiency and statistical rigour of post-release monitoring strategies.
Simulating the effects of clumped egg laying on mosquito population dynamics in relation to gene-drive interventions
3999Morris, ALF, N.; Ghani, A., American Journal of Tropical Medicine and Hygiene, 99:279-280. 2018-01-17 00:00:00.
Gene-drive based vector control methods are a rapidly developing tool in the fight against malaria. They utilise highly targeted insertions of genes to express specific traits, such as biases in offspring sex ratio or inhibited vector competence, which are preferentially inherited by copying themselves between chromosomes. Although theoretically selfsustaining, most gene-drive methods are sensitive to numerous aspects of local mosquito population dynamics. Often however, due to gaps in our knowledge, mathematical modelling of gene drive systems makes highly simplifying assumptions about key aspects of mosquito ecology. There is an urgent need to better understand fine scale population processes to improve predictions of the likely impact of gene-drive releases and refine development of target product profiles. The principal drivers of local mosquitoes dynamics can be traced to the larval stages, where density-dependent mortality in larval habitats is a key regulator of local adult density. In this study, we explored these drivers by simulating non-homogenous egg-laying over time and analysing its relationship with differing functional forms of density dependence. We developed a discrete-time stochastic model of mosquito population dynamics, which incorporated the random, temporal clumping of egg laying. The model was fitted to historical longitudinal mosquito trapping data using advanced particle MCMC methods. From this we were able to better quantify the relationship between clumping of egg laying and densitydependent regulation of larval populations, and thus refine estimates of the mosquito reproduction number, Rm - a key determinant of the predicted impact of gene-drive interventions. We find incorporation of clumping of egg-laying improves model fit, and reduces estimates of Rm, thus making establishment and spread of gene-drive constructs more likely than predicted by models assuming higher Rm value.
The roles of ethics in gene drive research and governance
4019Thompson, PB, Journal of Responsible Innovation, 5:S159-S179. 2018-01-17 00:00:00.
Ethics research queries the norms and values that shape the goals and justification for gene drive projects, and that might lead to issue or opposition to such projects. A framework for organizing ethics research is offered. In addition to basic research ethics and risk assessment, gene drives will give rise to questions about the fiduciary responsibilities of scientists, democratizing technology, and the links between epistemology and social power relations. A final category of ethical issues covers the way in which research on norms and values is organized, funded and integrated into other aspects of a gene drive project.
Identifying knowledge gaps for gene drive research to control invasive animal species: The next CRISPR step
3998Moro, DB, Margaret; Kennedy, Malcolm; Campbell, Susan; Tizard, Mark, Global Ecology and Conservation, 13:e00363. 2018-01-16 00:00:00.
Invasive animals have been linked to the extinctions of native wildlife, and to significant agricultural financial losses or impacts. Current approaches to control invasive species require ongoing resources and management over large geographic scales, and often result in the short-term suppression of populations. New and innovative approaches are warranted. Recently, the RNA guided gene drive system based on CRISPR/Cas9 is being proposed as a potential gene editing tool that could be used by wildlife managers as a nonlethal addition or alternative to help reduce pest animal populations. While regulatory control and social acceptance are crucial issues that must be addressed, there is an opportunity now to identify the knowledge and research gaps that exist for some important invasive species. Here we systematically determine the knowledge gaps for pest species for which gene drives could potentially be applied. We apply a conceptual ecological risk framework within the gene drive context within an Australian environment to identify key requirements for undertaking work on seven exemplar invasive species in Australia. This framework allows an evaluation of the potential research on an invasive species of interest and within a gene drive and risk context. We consider the currently available biological, genetic and ecological information for the house mouse, European red fox, feral cat, European rabbit, cane toad, black rat and European starling to evaluate knowledge gaps and identify candidate species for future research. We discuss these findings in the context of future thematic areas of research worth pursuing in preparation for a more formal assessment of the use of gene drives as a novel strategy for the control of these and other invasive species.
Public engagement and communication: who is in charge?
3958Boëte, C, EMBO reports, 19:1. 2018-01-16 00:00:00.
The discovery of CRISPR has led to the development of gene drive systems that could be used to spread desired traits in a target species or to exterminate a population within a few generations. It is no surprise then that such a controversial and disruptive technology has raised hopes and fears regarding its application for public health, conservation, or agriculture. It has even prompted a call for a moratorium on genetically engineered gene drive last year that was signed by about 160 organizations (http://www.synbiowatch.org/gene-drives/gene-drives-moratorium/). In reaction to this call, an open letter was addressed to the Parties to the 13th meeting on the Convention on Biological Diversity (CBD) in December 2016 in Mexico and the Cartagena Protocol on Biosafety, requesting support on gene drive research. Interestingly, this call was presented on the website of Target Malaria (http://targetmalaria.org/open-letter/), a consortium that is developing a gene drive approach to suppress the populations of mosquito malaria vectors. About 80 scientists, most of whom are involved in insect research and malaria control, have signed this open letter. At the end, the call for a …
Switchable genome editing via genetic code expansion
4018Suzuki, TA, Maki; Patel, Sanjay G.; Luk, Louis Y. P.; Tsai, Yu-Hsuan; Perry, Anthony C. F., Scientific Reports, 8:10051. 2018-01-16 00:00:00.
Multiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clinical therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiological BOC incorporation such that Cas9 (Cas9BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geographical ranges.
Economic issues to consider for gene drives
3997Mitchell, PDB, Z.; McRoberts, N., Journal of Responsible Innovation, 5:S180-S202. 2018-01-15 00:00:00.
We examine four economic issues regarding gene drive applications made possible by gene editing technologies. First, whether gene drives are self-sustaining or self-limiting will largely determine which types of organizations have incentives to develop and deploy gene drives and greatly influence their governance and regulation. Social factors will also play key roles, particularly public perceptions, with these perceptions co-determined with regulation and governance. Second, gene drive applications will generate unintended negative social impacts that will partially offset benefits. Third, economic surplus, the traditional measure of economic benefits, incompletely captures the welfare impacts of gene drive applications. Fourth, gene drives imply dynamic nonlinearities that make identifying economic equilibria and general policy recommendations challenging. The potentially substantial benefits, coupled with the technical, social, and economic uncertainties surrounding gene drives, suggest that a responsible course of action is to move forward while maintaining regulatory flexibility and conducting research to resolve key uncertainties.
Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiae
3957Basgall, EMG, S. C.; Goeckel, M. E.; Giersch, R. M.; Roggenkamp, E.; Schrock, M. N.; Halloran, M.; Finnigan, G. C., Microbiology-Sgm, 164:464-474. 2018-01-15 00:00:00.
Given the widespread use and application of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas gene editing system across many fields, a major focus has been the development, engineering and discovery of molecular means to precisely control and regulate the enzymatic function of the Cas9 nuclease. To date, a variety of Cas9 variants and fusion assemblies have been proposed to provide temporally inducible and spatially controlled editing functions. The discovery of a new class of 'anti-CRISPR' proteins, evolved from bacteriophage in response to the prokaryotic nuclease-based immune system, provides a new platform for control over genomic editing. One Cas9-based application of interest to the field of population control is that of the 'gene drive'. Here, we demonstrate use of the AcrIIA2 and AcrIIA4 proteins to inhibit active gene drive systems in budding yeast. Furthermore, an unbiased mutational scan reveals that titration of Cas9 inhibition may be possible by modification of the anti-CRISPR primary sequence.
Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populations
3977Hammond, AMK, Kyros; Gribble, Matthew; Karlsson, Xenia; Morianou, Ioanna; Galizi, Roberto; Beaghton, Andrea; Crisanti, Andrea; Nolan, Tony, bioRxiv, 360339:1-16. 2018-01-15 00:00:00.
CRISPR-based genes drives bias their own inheritance and can be used to modify entire populations of insect vectors of disease as a novel form of sustainable disease control. Gene drives designed to interfere with female fertility can suppress populations of the mosquito vector of malaria, however laboratory demonstrations showed strong unintended fitness costs and high levels of resistant mutations that limited the potential of the first generation of gene drives to spread. We describe three new gene drives designed to restrict spatio-temporal nuclease expression by using novel regulatory sequences. Two of the three new designs dramatically improve fitness and mitigate the creation and selection of resistance. We dissect the relative contributions of germline CRISPR activity versus embryonic CRISPR activity resulting from parental deposition, showing that the improved performance of the new designs is due to tighter germline restriction of the nuclease activity and significantly lower rates of end-joining repair in the embryo. Moreover, we demonstrate in laboratory-contained population experiments that these gene drives show remarkably improved invasion dynamics compared to the first generation drives, resulting in greater than 90% suppression of the reproductive output and a delay in the emergence of target site resistance, even at a loosely constrained target sequence. These results illustrate important considerations for gene drive design and will help expedite the development of gene drives designed to control malaria transmission in Africa.
Kinetic basis for DNA target specificity of CRISPR-Cas12a
4017Strohkendl, IS, Fatema A.; Rybarski, James R.; Finkelstein, Ilya J.; Russell, Rick, Molecular Cell, 71:816-824. 2018-01-15 00:00:00.
Summary Class 2 CRISPR-Cas nucleases are programmable genome editing tools with promising applications in human health and disease. However, DNA cleavage at off-target sites that resemble the target sequence is a pervasive problem that remains poorly understood mechanistically. Here, we use quantitative kinetics to dissect the reaction steps of DNA targeting by Acidaminococcus sp Cas12a (also known as Cpf1). We show that Cas12a binds DNA tightly in two kinetically separable steps. Protospacer-adjacent motif (PAM) recognition is followed by rate-limiting R-loop propagation, leading to inevitable DNA cleavage of both strands. Despite functionally irreversible binding, Cas12a discriminates strongly against mismatches along most of the DNA target sequence. This result implies substantial reversibility during R-loop formation—a late transition state—and defies common descriptions of a “seed” region. Our results provide a quantitative basis for the DNA cleavage patterns measured in vivo and observations of greater reported target specificity for Cas12a than for the Cas9 nuclease.
Anticipating complexity in the deployment of gene drive insects in agriculture
3956Baltzegar, JCB, Jessica; Elsensohn, Johanna E.; Gutzmann, Nicole; Jones, Michael S.; King, Sheron; Sudweeks, Jayce, Journal of Responsible Innovation, 5:S81-S97. 2018-01-14 00:00:00.
Insects cause substantial losses to agricultural crops each yearand require intensive management approaches. Genetic pestmanagement has emerged as a viable, non-chemical alternative formanaging insect pests. The development of engineered genedrives for agricultural use is promising, though unproven, and hasthe potential to impact farmers as well as broader socio-ecologicalsystems in several ways. Drawing on lessons from the deploymentof other pest control technologies, this paper considers howinsects containing gene drives could intersect with some of thecomplexities that characterize agricultural systems. Gene drives arebeing developed in a landscape of pest management shaped bypast and current approaches, experiences, regulations, publicopinion, and pest invasions. Because gene drive insects may spreadwell beyond their release area, stakeholder groups at differentspatial scales need to be engaged in decisions about theirdeployment. This new paradigm both complicates and offers greatpromise for future pest management efforts
Harnessing gene drive
3996Min, JS, Andrea L.; Najjar, Devora; Esvelt, Kevin M., Journal of Responsible Innovation, 5:S40-S65. 2018-01-14 00:00:00.
When scientists alter the genome of an organism, we typically reduce its ability to reproduce in the wild. This limitation has prevented researchers from rendering wild insects unable to spread disease, programing pests to ignore our crops, using genetics to precisely remove environmentally damaging invasive species, and much more. Gene drive occurs when a vertically transmitted genetic element reliably spreads through a population over generations despite providing no reproductive advantage to each host organism. Until recently, scientific efforts to take advantage of this natural phenomenon achieved only limited success. The advent of CRISPR genome editing has dramatically accelerated efforts to harness gene drive. Small groups of scientists may now be capable of unilaterally altering entire wild populations, and through them, the shared environment. Determining whether, when, and how to develop gene drive interventions responsibly will be a defining challenge of our time. Here we describe capabilities, safeguards, applications, and opportunities relevant to gene drive technologies.
Selfish genetic elements
3955Agren, JAC, A. G., PLOS Genetics, 14:20. 2018-01-13 00:00:00.
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative effect on organismal fitness. [1-6] Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism. However, when genes have some control over their own transmission, the rules can change, and so just like all social groups, genomes are vulnerable to selfish behaviour by their parts. Early observations of selfish genetic elements were made almost a century ago, but the topic did not get widespread attention until several decades later. Inspired by the gene-centred views of evolution popularized by George Williams[7] and Richard Dawkins,[8] two papers were published back-to-back in Nature in 1980-by Leslie Orgel and Francis Crick[9] and Ford Doolittle and Carmen Sapienza[10] respectively-introducing the concept of selfish genetic elements (at the time called "selfish DNA") to the wider scientific community. Both papers emphasized that genes can spread in a population regardless of their effect on organismal fitness as long as they have a transmission advantage. Selfish genetic elements have now been described in most groups of organisms, and they demonstrate a remarkable diversity in the ways by which they promote their own transmission.[11] Though long dismissed as genetic curiosities, with little relevance for evolution, they are now recognized to affect a wide swath of biological processes, ranging from genome size and architecture to speciation.[12]
Strengthening regulatory capacity for gene drives in Africa: leveraging NEPAD’s experience in establishing regulatory systems for medicines and GM crops in Africa
3975Glover, BA, Olalekan; Savadogo, Moussa; Timpo, Samuel; Lemgo, Godwin; Sinebo, Woldeyesus; Akile, Sunday; Obukosia, Silas; Ouedraogo, Jeremy; Ndomondo-Sigonda, Margareth; Koch, Muffy; Makinde, Diran; Ambali, Aggrey, BMC Proceedings, 12:1-10. 2018-01-13 00:00:00.
The New Partnership for Africa’s Development (NEPAD) Agency recognizes that Africa is in a period of transition and that this demands exploring and harnessing safe advances made in science-based innovations including modern biotechnology. To advance the science of biotechnology in Africa effectively, while at the same time safeguarding human health and the environment, the African Union (AU) adopted a High-Level Panel report on modern biotechnology entitled, Freedom to Innovate, which advocated for a coevolutionary approach where technology development goes hand in hand with regulation. Furthermore, most AU member states are Parties to the Cartagena Protocol on Biosafety (CPB), a legally binding international agreement negotiated, concluded and adopted within the framework of the Convention on Biological Diversity. This seeks to guide Parties in developing systems for the environmentally sound management of modern biotechnology applications. Currently, 49 AU Member States have signed and ratified the CPB, of which 12 have passed biosafety laws. African Union (AU) member states are at different stages in the development of regulatory frameworks for applications of modern biotechnology, which include genetically modified (GM) products and other emerging technologies. Biosafety regulatory frameworks comprise: biotechnology and/or biosafety policy; laws, regulations and guidelines; administrative systems; decision-making systems; and mechanisms for public engagement. To assist Member States to implement functional regulatory frameworks for both agriculture and health applications, the NEPAD Agency established the African Biosafety Network of Expertise (ABNE) and the African Medicines Regulatory Harmonization (AMRH). Currently, transgenic insects and GM crops are regulated by Competent National Authorities whose mandate derives from national biosafety laws. For GM crops, a lot of research has been conducted up to the confined field trial (CFT) and multi-location trials stages in a number of African countries. Burkina Faso has fully functional containment facilities for transgenic mosquitoes while Mali and Uganda are developing theirs. The Burkina Faso regulatory agency has granted permits and has already received sets of sterile mosquito eggs for trials in the contained facility. It is instructive to note that both ABNE and AMRH have worked with national and regional regulatory bodies in Africa to enhance their technical capacities for informed decision making, adoption of best practices, and compliance with international standards. It is against the backdrop of a rich blend of on-the-ground knowledge, experience, expertise, and insight into the context and political sensitivities of member states that the NEPAD Agency seeks to expand existing support. This would include capacity strengthening in the regulation of emerging technologies, such as the application of gene drives in the development of transgenic mosquito for the control of malaria transmission.
To reduce the global burden of human schistosomiasis, use ‘old fashioned’ snail control
4015Sokolow, SHW, Chelsea L.; Jones, Isabel J.; Lafferty, Kevin D.; Kuris, Armand; Hsieh, Michael H.; De Leo, Giulio A., Trends in Parasitology, 34:23-40. 2018-01-13 00:00:00.
Control strategies to reduce human schistosomiasis have evolved from ‘snail picking’ campaigns, a century ago, to modern wide-scale human treatment campaigns, or preventive chemotherapy. Unfortunately, despite the rise in preventive chemotherapy campaigns, just as many people suffer from schistosomiasis today as they did 50 years ago. Snail control can complement preventive chemotherapy by reducing the risk of transmission from snails to humans. Here, we present ideas for modernizing and scaling up snail control, including spatiotemporal targeting, environmental diagnostics, better molluscicides, new technologies (e.g., gene drive), and ‘outside the box’ strategies such as natural enemies, traps, and repellants. We conclude that, to achieve the World Health Assembly’s stated goal to eliminate schistosomiasis, it is time to give snail control another look.
Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectors
3974Edgington, MPA, Luke S., PLOS Computational Biology, 14:e1006059. 2018-01-12 00:00:00.
Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne diseases are currently being investigated. Among the promising techniques currently being considered are a range of genetic control methods known as gene drive systems. These allow desirable genetic traits (such as a much reduced capacity for vectors to transmit viruses) to be spread through a target population; taking advantage of natural mate seeking behaviour to locate vector sub-populations that can be extremely difficult for humans to locate and reach. Here we use mathematical models (parameterised to consider mosquito populations) to demonstrate the robustness of the engineered underdominance and killer-rescue classes of gene drive to different ecological factors including birth and death rates; the number and quality of breeding sites (i.e. carrying capacity); and the strength of density-dependent competition during the larval development phase. We then go on to explore the range of potential outcomes that may result from the migration of individuals between two neighbouring populations.
Synthetic gene drive: between continuity and novelty: Crucial differences between gene drive and genetically modified organisms require an adapted risk assessment for their use
4014Simon, SO, Mathias; Engelhard, Margret, EMBO Reports, 19:e45760. 2018-01-12 00:00:00.
Gene drive organisms differ from “classical” genetically modified organisms in several crucial aspects. It would require new approaches for risk assessment to gauge their potential impact on the environment. While some argue that current risk assessment frameworks can accommodate synthetic gene drives, others call for a moratorium owing to gene drives’ potentially detrimental impact on wildlife
A CRISPR–Cas9-based gene drive platform for genetic interaction analysis in Candida albicans
4013Shapiro, RSC, Alejandro; Porter, Caroline B. M.; Hamblin, Meagan; Kaas, Christian S.; DiCarlo, James E.; Zeng, Guisheng; Xu, Xiaoli; Revtovich, Alexey V.; Kirienko, Natalia V.; Wang, Yue; Church, George M.; Collins, James J., Nature Microbiology, 3:73-82. 2018-01-11 00:00:00.
Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR–Cas9-based ‘gene drive array’ platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants. We generate double-gene deletion libraries to demonstrate this technology, targeting antifungal efflux and biofilm adhesion factors. We screen these libraries to identify virulence regulators and determine how genetic networks shift under diverse conditions. This platform transforms our ability to perform genetic interaction analysis in C. albicans and is readily extended to other fungal pathogens.
Genetically engineered mosquitoes, Zika and other arboviruses, community engagement, costs, and patents: Ethical issues
3993Meghani, ZB, Christophe, PLOS Neglected Tropical Diseases, 12:e0006501. 2018-01-11 00:00:00.
We discuss here key ethical questions raised by the use of GE insects, with the aim of fostering discussion between the public, researchers, policy makers, healthcare organizations, and regulatory agencies at the local, national, and international levels. We affect that goal by outlining a procedural approach to decision-making about the use of the biotechnology that goes beyond community engagement. The protocol we advocate for entails informed deliberations and decision-making at the community level. It is designed to ensure that the voices of the marginalized and vulnerable groups that would be disproportionately affected by the decision are heard during the community-wide discussions. Moreover, we make the case that the values embedded in the risk assessment should be identified so that the community can make an informed decision about the use of GE insects. In addition, we advocate for the involvement of a variety of actors whose responsibility would be to ensure that the community has the opportunity to make an informed decision based on deliberations about the use of the biotechnology.
CRISPR-based gene drives for pest control
3992McFarlane, GRW, C. Bruce A.; Lillico, Simon G., Trends in Biotechnology, 36:130-133. 2018-01-10 00:00:00.
Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene drives (GDs) could be used to spread desirable genetic elements through wild populations. With the imminent development of this technology in vertebrates, we believe that it is timely to highlight two forms of sex-ratio distorting GDs that show potential as pest management tools.
Invasion and migration of spatially self-limiting gene drives: A comparative analysis
3972Dhole, S.; Vella, M. R; Lloyd, A. L.; Gould, F., Evolutionary Applications, 11:794-808. 2018-01-10 00:00:00.
Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self?limiting. Here, we use a population genetics model to compare the expected characteristics of three spatially self?limiting gene drive systems: one?locus underdominance, two?locus underdominance and daisy?chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy?chain system is the most efficient, requiring the smallest release, followed by the two?locus underdominance system, and then the one?locus underdominance system. However, when the target population exchanges migrants with a nontarget population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy?chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two?locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one?locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two?locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy?chain system can, for a small set of parameter values, achieve a temporally limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.
Can CRISPR-based gene drive be confined in the Wild? A question for molecular and population biology
3991Marshall, JMA, Omar S., ACS Chemical Biology, 13:424-430. 2018-01-09 00:00:00.
The recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with greater ease. In order for the benefits of this technology to be realized, in some circumstances drive systems should be developed that are capable of both spreading into populations to achieve their desired impact and being recalled in the event of unwanted consequences or public disfavor. We review the performance of three broad categories of drive systems at achieving these goals: threshold-dependent drives, homing-based drive and remediation systems, and temporally self-limiting systems such as daisy-chain drives.
Gene drives in our future: challenges of and opportunities for using a self-sustaining technology in pest and vector management
3971Collins, JP, BMC Proceedings, 12:9. 2018-01-09 00:00:00.
Gene drives are systems of biased inheritance that enhance the likelihood a sequence of DNA passes between generations through sexual reproduction and potentially throughout a local population and ultimately all connected populations of a species. Gaps in our knowledge of gene drive systems prompted the US National Institutes of Health (NIH) and the Foundation for the NIH to ask the US National Academies of Sciences, Engineering, and Medicine (NASEM) to convene an expert panel to provide an independent, objective examination of what we know about gene drive systems. The report, “Gene drives on the horizon: Advancing science, navigating uncertainty, and aligning research with public values,” outlines our understanding of the science, ethics, public engagement, governance, and risk assessment pertaining to gene drive research.
Development of a multi-locus CRISPR gene drive system in budding yeast
4029Yan, YF, Gregory C., Scientific reports, 8:17277-17277. 2018-01-07 00:00:00.
The discovery of CRISPR/Cas gene editing has allowed for major advances in many biomedical disciplines and basic research. One arrangement of this biotechnology, a nuclease-based gene drive, can rapidly deliver a genetic element through a given population and studies in fungi and metazoans have demonstrated the success of such a system. This methodology has the potential to control biological populations and contribute to eradication of insect-borne diseases, agricultural pests, and invasive species. However, there remain challenges in the design, optimization, and implementation of gene drives including concerns regarding biosafety, containment, and control/inhibition. Given the numerous gene drive arrangements possible, there is a growing need for more advanced designs. In this study, we use budding yeast to develop an artificial multi-locus gene drive system. Our minimal setup requires only a single copy of S. pyogenes Cas9 and three guide RNAs to propagate three gene drives. We demonstrate how this system could be used for targeted allele replacement of native genes and to suppress NHEJ repair systems by modifying DNA Ligase IV. A multi-locus gene drive configuration provides an expanded suite of options for complex attributes including pathway redundancy, combatting evolved resistance, and safeguards for control, inhibition, or reversal of drive action.
Population dynamics of underdominance gene drive systems in continuous space
3969Champer, JZ, Joanna; Champer, Sam; Liu, Jingxian; Messer, Philipp W., bioRxiv, 449355:1-23. 2018-01-07 00:00:00.
Underdominance gene drive systems promise a mechanism for rapidly spreading payload alleles through a local population while otherwise remaining confined, unable to spread into neighboring populations due to their frequency-dependent dynamics. Such systems could provide a new tool in the fight against vector-borne diseases by disseminating transgenic payloads through vector populations. If local confinement can indeed be achieved, the decision-making process for the release of such constructs would likely be considerably simpler compared to other gene drive mechanisms such as CRISPR homing drives. So far, the confinement ability of underdominance systems has only been demonstrated in models of panmictic populations linked by migration. How such systems would behave in realistic populations where individuals move over continuous space remains largely unknown. Here, we study several underdominance systems in continuous-space population models and show that their dynamics are drastically altered from those in panmictic populations. Specifically, we find that all underdominance systems we studied can fail to persist in such environments, even after successful local establishment. At the same time, we find that a two-locus two-toxin-antitoxin system can still successfully invade neighboring populations in many scenarios even under weak migration. This suggests that the parameter space for underdominance systems to both establish in a given region and remain confined to that region would likely be highly limited. Overall, these results indicate that spatial context must be considered when assessing strategies for the deployment of underdominance systems.
Recent advances in threshold-dependent gene drives for mosquitoes
3989Leftwich, PTE, Matthew P.; Harvey-Samuel, Tim; Carabajal Paladino, Leonela Z.; Norman, Victoria C.; Alphey, Luke, Biochemical Society Transactions, 46:1203-1212. 2018-01-07 00:00:00.
Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity and mortality around the world. Recent advances in gene drives have produced control methods that could theoretically modify all populations of a disease vector, from a single release, making whole species less able to transmit pathogens. This ability has caused both excitement, at the prospect of global eradication of mosquito-borne diseases, and concern around safeguards. Drive mechanisms that require individuals to be released at high frequency before genes will spread can therefore be desirable as they are potentially localised and reversible. These include underdominance-based strategies and use of the reproductive parasite Wolbachia. Here, we review recent advances in practical applications and mathematical analyses of these threshold-dependent gene drives with a focus on implementation in Aedes aegypti, highlighting their mechanisms and the role of fitness costs on introduction frequencies. Drawing on the parallels between these systems offers useful insights into practical, controlled application of localised drives, and allows us to assess the requirements needed for gene drive reversal.CI, cytoplasmic incompatibility; UD, underdominance; UDMEL, maternal-effect lethal underdominance
Tuning CRISPR-Cas9 gene grives in Saccharomyces cerevisiae
4009Roggenkamp, EG, Rachael M.; Schrock, Madison N.; Turnquist, Emily; Halloran, Megan; Finnigan, Gregory C., G3-Genes Genomes Genetics, 8:999. 2018-01-07 00:00:00.
Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based “gene drive,” allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component—Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions—to modulate drive activity within a population.
Reducing resistance allele formation in CRISPR gene drive
3968Champer, JL, Jingxian; Oh, Suh Yeon; Reeves, Riona; Luthra, Anisha; Oakes, Nathan; Clark, Andrew G.; Messer, Philipp W., Proceedings of the National Academy of Sciences of the United States of America, 115:5522-5527. 2018-01-06 00:00:00.
A functioning gene drive mechanism could fundamentally change our strategies for the control of vector-borne diseases, such as malaria, dengue, and Zika. CRISPR homing gene drive promises such a mechanism, which could be used to rapidly spread genetic modifications among the mosquitoes that transmit these diseases. However, recent studies have shown that current drives would likely be unable to spread in insect populations due to the high rate at which resistance will evolve. In this study, we provide an experimental demonstration that guide RNA multiplexing can successfully reduce resistance rates but also find that such an approach would still need to be combined with additional strategies to create drives that are efficient enough for use in wild populations.CRISPR homing gene drives can convert heterozygous cells with one copy of the drive allele into homozygotes, thereby enabling super-Mendelian inheritance. Such a mechanism could be used, for example, to rapidly disseminate a genetic payload in a population, promising effective strategies for the control of vector-borne diseases. However, all CRISPR homing gene drives studied in insects thus far have produced significant quantities of resistance alleles that would limit their spread. In this study, we provide an experimental demonstration that multiplexing of guide RNAs can both significantly increase the drive conversion efficiency and reduce germline resistance rates of a CRISPR homing gene drive in Drosophila melanogaster. We further show that an autosomal drive can achieve drive conversion in the male germline, with no subsequent formation of resistance alleles in embryos through paternal carryover of Cas9. Finally, we find that the nanos promoter significantly lowers somatic Cas9 expression compared with the vasa promoter, suggesting that nanos provides a superior choice in drive strategies where gene disruption in somatic cells could have fitness costs. Comparison of drive parameters among the different constructs developed in this study and a previous study suggests that, while drive conversion and germline resistance rates are similar between different genomic targets, embryo resistance rates can vary significantly. Taken together, our results mark an important step toward developing effective gene drives capable of functioning in natural populations and provide several possible avenues for further control of resistance rates.
RPM-Drive: A robust, safe, and reversible gene drive system that remains functional after 200+ generations
4008Reed, FAA-M, Todd G.; Costantini, Maria S.; Láruson, Áki J.; Sutton, Jolene T., arXiv, 1806.05304:1-19. 2018-01-06 00:00:00.
Despite the advent of several novel, synthetic gene drive mechanisms and their potential to one-day control a number of devastating diseases, among other applications, practical use of these systems remains contentious and risky. In particular, there is little in the way of empirical evidence of the long-term robustness of these synthetic systems against mutational breakdown. Rather, most existing systems are either known or predicted to be susceptible to rapid inactivation, though methodological designs continue to be refined. Here we evaluate a currently existing synthetic, underdominance-based gene drive system 200+ generations after it was first established in a laboratory colony of Drosophila melanogaster. Not only do we find that the system is still functioning as designed, we also show evidence that disruptions to the genetic construct are highly likely to be removed by natural selection, contributing to the system's robust, long-term stability. This stability appears to be a result of a fundamental relationship between ribosomal proteins (a novel target of the system) and natural cellular defenses that protect against cancer development. As far as we are aware, this is the longest continually functioning synthetic gene drive system thus verified, making it highly appropriate for additional research into its eventual suitability for field trials. Due to inherent properties of this gene drive, it is also likely to be adaptable for use in many different species. The insect lines established and used to test this system have been deposited at a Drosophila stock center, and are available to labs for further, independent testing.
The use of driving endonuclease genes to suppress mosquito vectors of malaria in temporally variable environments
3988Lambert, BN, Ace; Burt, Austin; Godfray, H. Charles J., Malaria Journal, 17:154. 2018-01-06 00:00:00.
The use of gene drive systems to manipulate populations of malaria vectors is currently being investigated as a method of malaria control. One potential system uses driving endonuclease genes (DEGs) to spread genes that impose a genetic load. Previously, models have shown that the introduction of DEG-bearing mosquitoes could suppress or even extinguish vector populations in spatially-heterogeneous environments which were constant over time. In this study, a stochastic spatially-explicit model of mosquito ecology is combined with a rainfall model which enables the generation of a variety of daily precipitation patterns. The model is then used to investigate how releases of a DEG that cause a bias in population sex ratios towards males are affected by seasonal or random rainfall patterns. The parameters of the rainfall model are then fitted using data from Bamako, Mali, and Mbita, Kenya, to evaluate release strategies in similar climatic conditions.
A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes
3987Kyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea, Nature Biotechnology, 36:1062–1066. 2018-01-05 00:00:00.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all Anopheles mosquitoes so far analyzed. We found that CRISPR–Cas9-targeted disruption of the intron 4–exon 5 boundary aimed at blocking the formation of functional AgdsxF did not affect male development or fertility, whereas females homozygous for the disrupted allele showed an intersex phenotype and complete sterility. A CRISPR–Cas9 gene drive construct targeting this same sequence spread rapidly in caged mosquitoes, reaching 100% prevalence within 7–11 generations while progressively reducing egg production to the point of total population collapse. Owing to functional constraint of the target sequence, no selection of alleles resistant to the gene drive occurred in these laboratory experiments. Cas9-resistant variants arose in each generation at the target site but did not block the spread of the drive.
Catch me if you can: A spatial model for a brake-driven gene drive reversal
3967Calvez, V,,Debarre, F., Girardin, Leo, arXiv, 1812.06641:1-30. 2018-01-05 00:00:00.
We successfully prove that, whenever the drive fitness is at most 50% of the wild-type one while the brake fitness is close to the wild-type one, co-extinction of the brake and the drive occurs in the long run.
Rationally-engineered reproductive barriers using CRISPR & CRISPRa: an evaluation of the synthetic species concept in Drosophila melanogaster
4027Waters, AJC, Paolo; Gaboriau, David C. A.; Papathanos, Philippos Aris; Windbichler, Nikolai, Scientific Reports, 8:13125. 2018-01-05 00:00:00.
The ability to erect rationally-engineered reproductive barriers in animal or plant species promises to enable a number of biotechnological applications such as the creation of genetic firewalls, the containment of gene drives or novel population replacement and suppression strategies for genetic control. However, to date no experimental data exist that explores this concept in a multicellular organism. Here we examine the requirements for building artificial reproductive barriers in the metazoan model Drosophila melanogaster by combining CRISPR-based genome editing and transcriptional transactivation (CRISPRa) of the same loci. We directed 13 single guide RNAs (sgRNAs) to the promoters of 7 evolutionary conserved genes and used 11 drivers to conduct a misactivation screen. We identify dominant-lethal activators of the eve locus and find that they disrupt development by strongly activating eve outside its native spatio-temporal context. We employ the same set of sgRNAs to isolate, by genome editing, protective INDELs that render these loci resistant to transactivation without interfering with target gene function. When these sets of genetic components are combined we find that complete synthetic lethality, a prerequisite for most applications, is achievable using this approach. However, our results suggest a steep trade-off between the level and scope of dCas9 expression, the degree of genetic isolation achievable and the resulting impact on fly fitness. The genetic engineering strategy we present here allows the creation of single or multiple reproductive barriers and could be applied to other multicellular organisms such as disease vectors or transgenic organisms of economic importance.
Redkmer: An assembly-free pipeline for the identification of abundant and specific X-chromosome target sequences for X-shredding by CRISPR endonucleases
4006Papathanos, PAW, Nikolai, CRISPR Journal, 1:88-98. 2018-01-04 00:00:00.
CRISPR-based synthetic sex ratio distorters, which operate by shredding the X-chromosome during male meiosis, are promising tools for the area-wide control of harmful insect pest or disease vector species. X-shredders have been proposed as tools to suppress insect populations by biasing the sex ratio of the wild population toward males, thus reducing its natural reproductive potential. However, to build synthetic X-shredders based on CRISPR, the selection of gRNA targets, in the form of high-copy sequence repeats on the X chromosome of a given species, is difficult, since such repeats are not accurately resolved in genome assemblies and cannot be assigned to chromosomes with confidence. We have therefore developed the redkmer computational pipeline, designed to identify short and highly abundant sequence elements occurring uniquely on the X chromosome. Redkmer was designed to use as input minimally processed whole genome sequence data from males and females. We tested redkmer with short- and long-read whole genome sequence data of Anopheles gambiae, the major vector of human malaria, in which the X-shredding paradigm was originally developed. Redkmer established long reads as chromosomal proxies with excellent correlation to the genome assembly and used them to rank X-candidate kmers for their level of X-specificity and abundance. Among these, a high-confidence set of 25-mers was identified, many belonging to previously known X-chromosome repeats of Anopheles gambiae,including the ribosomal gene array and the selfish elements harbored within it. Data from a control strain, in which these repeats are shared with the Y chromosome, confirmed the elimination of these kmers during filtering. Finally, we show that redkmer output can be linked directly to gRNA selection and off-target prediction. In addition, the output of redkmer, including the prediction of chromosomal origin of single-molecule long reads and chromosome specific kmers, could also be used for the characterization of other biologically relevant sex chromosome sequences, a task that is frequently hampered by the repetitiveness of sex chromosome sequence content.
Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs
4005Oberhofer, GI, Tobin; Hay, Bruce A., Proceedings of the National Academy of Sciences of the United States of America, 115:e9343. 2018-01-03 00:00:00.
Homing endonuclease gene (HEG)-based gene drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies are vulnerable to failure through mechanisms that create alleles resistant to cleavage but that retain wild-type gene function. We show that resistance allele creation can be prevented through the use of guide RNAs designed to cleave a gene at four target sites. However, homing rates were modest, and the HEGs were unstable during homing. In addition, use of a promoter active in the female germline resulted in levels of HEG carryover that compromised the viability or fertility of HEG-bearing heterozygotes, thereby preventing drive. We propose strategies that can help to overcome these problems in next-generation HEG systems.A gene drive method of particular interest for population suppression utilizes homing endonuclease genes (HEGs), wherein a site-specific, nuclease-encoding cassette is copied, in the germline, into a target gene whose loss of function results in loss of viability or fertility in homozygous, but not heterozygous, progeny. Earlier work in Drosophila and mosquitoes utilized HEGs consisting of Cas9 and a single guide RNA (gRNA) that together target a specific gene for cleavage. Homing was observed, but resistant alleles immune to cleavage, while retaining wild-type gene function, were also created through nonhomologous end joining. Such alleles prevent drive and population suppression. Targeting a gene for cleavage at multiple positions has been suggested as a strategy to prevent the appearance of resistant alleles. To test this hypothesis, we generated two suppression HEGs in Drosophila melanogaster targeting genes required for embryonic viability or fertility, using a HEG consisting of CRISPR/Cas9 and gRNAs designed to cleave each gene at four positions. Rates of target locus cleavage were very high, and multiplexing of gRNAs prevented resistant allele formation. However, germline homing rates were modest, and the HEG cassette was unstable during homing events, resulting in frequent partial copying of HEGs that lacked gRNAs, a dominant marker gene, or Cas9. Finally, in drive experiments, the HEGs failed to spread due to the high fitness load induced in offspring as a result of maternal carryover of Cas9/gRNA complex activity. Alternative design principles are proposed that may mitigate these problems in future gene drive engineering.
Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management
3985Carrami, Eli M., ME, Kolja N.; Ahmed, Hassan M. M.; Sánchez C., Héctor M.; Dippel, Stefan; Marshall, John M.; Wimmer, Ernst A., Proceedings of the National Academy of Sciences of the United States of America, 115:6189-6194. 2018-01-03 00:00:00.
Resistance evolution caused by CRISPR/Cas9 gene-drive systems has a major impact on both the future scientific design of such gene-drive systems and on the politics of regulating experimentation and use of such systems. In our study, we show that in-frame drive-resistant alleles can be produced readily and inherently in a suppression gene-drive system. The rate at which such alleles emerge will determine the maximum size of the population that could be targeted for collapse and elimination. Here, we provide a potential target site and the modeling framework for implementation and optimization of a suppression gene-drive strategy to control Mediterranean fruit fly populations.The use of a site-specific homing-based gene drive for insect pest control has long been discussed, but the easy design of such systems has become possible only with the recent establishment of CRISPR/Cas9 technology. In this respect, novel targets for insect pest management are provided by new discoveries regarding sex determination. Here, we present a model for a suppression gene drive designed to cause an all-male population collapse in an agricultural pest insect. To evaluate the molecular details of such a sex conversion-based suppression gene drive experimentally, we implemented this strategy in Drosophila melanogaster to serve as a safe model organism. We generated a Cas9-based homing gene-drive element targeting the transformer gene and showed its high efficiency for sex conversion from females to males. However, nonhomologous end joining increased the rate of mutagenesis at the target site, which resulted in the emergence of drive-resistant alleles and therefore curbed the gene drive. This confirms previous studies that simple homing CRISPR/Cas9 gene-drive designs will be ineffective. Nevertheless, by performing population dynamics simulations using the parameters we obtained in D. melanogaster and by adjusting the model for the agricultural pest Ceratitis capitata, we were able to identify adequate modifications that could be successfully applied for the management of wild Mediterranean fruit fly populations using our proposed sex conversion-based suppression gene-drive strategy.
Self-limiting population genetic control with sex-linked genome editors
3965Burt, AD, Anne, Proceedings of the Royal Society B: Biological Sciences, 285:20180776. 2018-01-03 00:00:00.
In male heterogametic species the Y chromosome is transmitted solely from fathers to sons, and is selected for based only on its impacts on male fitness. This fact can be exploited to develop efficient pest control strategies that use Y-linked editors to disrupt the fitness of female descendants. With simple population genetic and dynamic models we show that Y-linked editors can be substantially more efficient than other self-limiting strategies and, while not as efficient as gene drive approaches, are expected to have less impact on non-target populations with which there is some gene flow. Efficiency can be further augmented by simultaneously releasing an autosomal X-shredder construct, in either the same or different males. Y-linked editors may be an attractive option to consider when efficient control of a species is desired in some locales but not others.
Gene drive: Evolved and synthetic
3964Burt, AC, Andrea, ACS Chemical Biology, 13:343-346. 2018-01-02 00:00:00.
Drive is a process of accelerated inheritance from one generation to the next that allows some genes to spread rapidly through populations even if they do not contribute to—or indeed even if they detract from—organismal survival and reproduction. Genetic elements that can spread by drive include gametic and zygotic killers, meiotic drivers, homing endonuclease genes, B chromosomes, and transposable elements. The fact that gene drive can lead to the spread of fitness-reducing traits (including lethality and sterility) makes it an attractive process to consider exploiting to control disease vectors and other pests. There are a number of efforts to develop synthetic gene drive systems, particularly focused on the mosquito-borne diseases that continue to plague us.
Community engagement and field trials of genetically modified insects and animals
5913Neuhaus, C. P., Hastings Center Report, 48:25-36. 2018-01-01 16:29:11.
New techniques for the genetic modification of organisms are creating new strategies for addressing persistent public health challenges. For example, the company Oxitec has conducted field trials internationally?and has attempted to conduct field trials in the United States?of a genetically modified mosquito that can be used to control dengue, Zika, and some other mosquito-borne diseases. In 2016, a report commissioned by the National Academies of Sciences, Engineering, and Medicine discussed the potential benefits and risks of another strategy, using gene drives. Driving a desired genotype through a population of wild animals or insects could lead to irreversible genetic modification of an entire species. The NASEM report recommends community, stakeholder, and public engagement about potential uses of the technology, and it argues that the engagement should occur as research advances, well before gene drives are deployed. Yet what ?engagement? means in practice is unclear. This article seeks clarity on this problem by offering a justification for community engagement and drawing out implications of this argument for the implementation and desired outcomes of community engagement. Community engagement is essential when it comes to research that would release genetically modified insects or animals into the environment. By contrast, obtaining informed consent from people who live near such a proposed field trial is neither necessary nor sufficient. Drawing on the epistemic and moral arguments for deliberative democracy, I propose two discrete mechanisms of community engagement: community advisory boards and deliberative forums, neither of which has been systematically incorporated into research governance. The proposed mechanisms would engender respect for persons who live near field trials, even when the results of deliberation override some individuals? preferences. Community engagement foregrounds the community in our thinking about humans? relationship to nature, and it implies that deciding to release genetically modified insects or animals into the wild ought to be a collective decision, not one made by product developers, policy-makers, private companies, research funders, or scientists alone.
Making policies about emerging technologies
5909Kaebnick, G. E. and M. K. Gusmano, Hastings Center Report, 48:S2-S11. 2018-01-01 16:23:19.
Can we make wise policy decisions about still-emerging technologies?decisions that are grounded in facts yet anticipate unknowns and promote the public's preferences and values? There is a widespread feeling that we should try. There also seems to be widespread agreement that the central element in wise decisions is the assessment of benefits and costs, understood as a process that consists, at least in part, in measuring, tallying, and comparing how different outcomes would affect the public interest. But how benefits and costs are best weighed when making decisions about whether to move forward with an emerging technology is not clear. Many commentators feel that the weighing is often inadequate or inappropriate. Those who argue for a ?precautionary? approach to the weighing do so precisely because they feel the need for a restraint on the dominant decision-making tools and processes for assessing outcomes. This Hastings Center special report examines those tools and processes, taking the method known as cost-benefit analysis as a starting point. In U.S. governance, CBA, sometimes informed by risk assessment, is the most widely used and extensively studied method, and authoritative reports on genetic and reproductive technologies often use language suggestive of cost-benefit analysis. There is also a long-running debate about the role of values in CBA and other formal impact assessment mechanisms?and about how those mechanisms compare to the precautionary principle. The guiding idea in the report is to engage in a close examination of the strengths and limits of CBA for ensuring that emerging technologies are used in ways that square with the public's values, drawing on applications of synthetic biology to illustrate and sharpen the analysis and then considering corrections to CBA and some alternative methodologies that handle values differently.
Gene Drives Can Wipe Out Entire Species… Or Save Them
5516Gizmodo, 2017-12-17 19:16:41.
Bill Gates and other investors have poured millions into gene drives. So what is the technology and why are scientists worried about it?
Gene drives to fight malaria: current state and future directions
5600Hammond, A. M. and R. Galizi, Pathogens and Global Health, 111:412-423. 2017-12-17 15:55:06.
Self-propagating gene drive technologies have a number of desirable characteristics that warrant their development for the control of insect pest and vector populations, such as the malaria-transmitting mosquitoes. Theoretically easy to deploy and self-sustaining, these tools may be used to generate cost-effective interventions that benefit society without obvious bias related to wealth, age or education. Their species-specific design offers the potential to reduce environmental risks and aim to be compatible and complementary with other control strategies, potentially expediting the elimination and eradication of malaria. A number of strategies have been proposed for gene-drive based control of the malaria mosquito and recent demonstrations have shown proof-of-principle in the laboratory. Though several technical, ethical and regulatory challenges remain, none appear insurmountable if research continues in a step-wise and open manner.
Informed consent in field trials of gene-drive mosquitoes
15682P. A. Kolopack and J. V. Lavery, Gates Open Research, 2017-12-11 14:46:00.
We argue that informed consent from individual research participants in gene drive trials may be required: (1) when blood and other forms of clinical data are collected from them, as will likely be the case in some studies involving epidemiological endpoints, such as the incidence of new infections with dengue and malaria; (2) when they participate in social science and/or behavioral research involving the completion of surveys and questionnaires; or (3) when their home or property is accessed and the location recorded as a spatial variable for the release or collection of mosquitoes because the precise location of the household is important for entomological reasons and these data constitute identifiable private information at the household level. Importantly, most regulations and guidelines allow these requirements to be waived or modified, to various degrees, according to the judgment of Institutional Review Boards.
Conservation demands safe gene drive
13629K. M. Esvelt and N. J. Gemmell, PLOS Biology, 15:e2003850. 2017-11-16 14:03:39.
Here, we explore the risk of accidental spread posed by self-propagating gene drive technologies, highlight new gene drive designs that might achieve better outcomes, and explain why we need open and international discussions concerning a technology that could have global ramifications.
Could genetic engineering save the Galapagos?
14868S. S. Hall, Scientific American, 2017-11-01 19:26:09.
Campbell has been working on eradications in the Galápagos since 1997, including a 2006 campaign to remove all the feral goats and donkeys from Floreana. A decade later he’s a project manager with Island Conservation, and the most ambitious project on its agenda is once again on Floreana: to eradicate every single rat and mouse on the island.
The potential for the use of gene drives for pest control in New Zealand: a perspective
14253P. K. Dearden, N. J. Gemmell, O. R. Mercier, P. J. Lester, M. J. Scott, R. D. Newcomb, T. R. Buckley, J. M. E. Jacobs, S. G. Goldson and D. R. Penman, Journal of the Royal Society of New Zealand, 48:225-244. 2017-10-25 14:20:45.
Here we describe the current state of gene drive technologies and present a series of examples to examine the potential benefits and problems arising from gene drive approaches for pest control in New Zealand.
Using CRISPR-based gene drive for agriculture pest control
13621V. Courtier-Orgogozo, B. Morizot and C. Boëte, EMBO Reports, 18:1481. 2017-09-01 13:15:07.
The authors respond to comments to their publication 10.15252/embr.201744205
What’s the story with genetic pest management (GPM)?
11584K. Guthrie, Predator Free NZ, 2017-07-13 15:30:50.
Breakthrough genetic technologies are likely to play a key role in achieving a predator-free future. But it’s important that we understand what the various technologies are now – as they’re being developed – not when they’re about to be implemented. We need to debate the issues and become as informed as possible; to know if there are risks involved in particular techniques and what safeguards will be in place. We need to be able to make informed choices, once such choices become possible. Not all genetic techniques, for example, involve ‘genetic engineering’.
Current vector control challenges in the fight against malaria
16269G. Benelli and J. C. Beier, Acta Tropica, 174:91-96. 2017-07-07 16:47:31.
The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS.
ASSEMBLY OF THE UNION Twenty-Ninth Ordinary Session: DECISIONS, DECLARATIONS AND RESOLUTION
16078African Union, African Union, 2017-07-04 14:45:50.
Assembly/AU/Dec.649(XXIX): COMMITS to sustain the gains made in the fight against Malaria and monitor antimalarial drug resistance and insecticide resistance; COMMITS ALSO to invest in the development and regulation of the gene-drive technology as well as other new innovations including next generation insecticides for Indoor Residual Spraying and Long Lasting Insecticidal Nets, Rapid Diagnostic Tests and Artemisinin-based Combination Therapy for the elimination of malaria and REQUESTS the Commission, WHO and NEPAD Agency to support these initiatives;
CRISPR’s Gene Drive Could Revive Extinct Species–or Create New Ones | Jennifer Doudna
5522Jennifer Doudna, Big Think, 2017-06-26 19:28:41.
A leading gene editing scientist, Jennifer Doudna, discusses gene drive and their applications as well as de-extinction technologies.
Trends in the development of mammalian pest control technology in New Zealand
13735C. T. Eason, L. Shapiro, S. Ogilvie, C. King and M. Clout, New Zealand Journal of Zoology, 44:267-304. 2017-06-19 19:31:49.
The use of new toxins with advantages in specific settings should be complemented by improvements in resetting trap technology, barrier approaches, and novel biocontrol and genetic concepts. Sodium fluoroacetate (1080) and other important tools have been retained; we have the ingredients for transformational change, and new tools are emerging from a research and development pipeline. However, there has been limited practical experience with emerging technologies compared with traditional or 1080 baits.
Centre for Effective Altruism | Gene drive and the case for reforming research
5476K. Esvelt, N. Labenz, G. Church, Centre for Effective Altruism, 2017-06-17 17:50:19.
The wisdom with which we develop and deploy new technologies will define the future of our civilization. Why do we conduct reseearch in small teams of specialists who cannot reliably anticipate consequences on their own? Might it be better to share our best ideas and plans with others, actively inviting concerns, criticism, and possible improvements? Unfortunately, the current system has evolved to punish sharing. By highlighting the benefits of an open approach and the dangers of the status quo, gene drive may allow us to test a new approach and change the governing incentives. + Fireside Chat with George Church, Kevin Esvelt, Nathan Labenz
The use of gene editing to create gene drives for pest control in New Zealand
16070Royal Society Te Apārangi Gene Editing Panel, Royal Society of New Zealand, 2017-06-06 13:54:28.
to explore the implications of gene editing technology for New Zealand, the Royal Society Te Apārangi has convened a multidisciplinary panel of some of New Zealand’s leading experts to consider the social, cultural, legal and economic implications of revolutionary gene-editing technologies for New Zealand to: • Raise awareness of the scientific possibilities and associated public issues of new gene editing technologies to inform debate • Provide information and guidance for policy makers to address current and new issues needing to be clarified or resolved • Show where gene-editing applications are covered by established policies and regulations and where changes are needed • Provide a New Zealand perspective to the global discussion on this technology and identify where global consensus is important T
Agricultural pest control with CRISPR-based gene drive: time for public debate
13636V. Courtier-Orgogozo, B. Morizot and C. Boëte, EMBO Reports, 18:878-880. 2017-06-01 14:19:16.
Gene drive technology to control disease vectors or pests has great potential for addressing humanitarian and public health problems. Its application for pest control in agriculture, however, raises important environmental, social and ethical issues.
SCIENTIFIC OPINION: In response to the referral of 12 October 2015 concerning use of genetically modified mosquitoes for vector control
16065High Council for Biotechnology, High Council for Biotechnology (France), 2017-05-31 13:46:03.
The Scientific Committee’s opinion describes emerging vector control techniques using GM mosquitoes, the current state of research into and development of these techniques and the outcomes of initial experiments worldwide. To date, only one technique has been developed to an operational level: Oxitec’s RIDL technique, which sets out to reduce a mosquito population by repeated mass releases of sterilising transgenic males. Two other techniques at an earlier stage of research and development are based on gene drive, seeking to spread a genetic trait in a wild population, either to make the mosquitoes incapable of transmitting pathogens (gene drive for population modification) or to eliminate the population by spreading sterility (gene drive for population elimination).
Gene drive for Malaria control | Andrea Crisanti |
5519TEDx, 2017-04-04 19:23:37.
Andrea discusses his team's laboratory work that has developed a revolutionary technology to spread genetic modifications from few laboratory mosquitoes to wild populations to eradicate malaria in the near future
A Revolutionary Genetic Experiment is Planned for a West African Village – If Residents Agree
11446Ike Swetitz, STAT, 2017-03-14 18:05:29.
This small village of mud-brick homes in West Africa might seem the least likely place for an experiment at the frontier of biology. Yet scientists here are engaged in what could be the most promising, and perhaps one of the most frightening, biological experiments of our time. They are preparing for the possible release of swarms of mosquitoes that, until now, have been locked away in a research lab behind double metal doors and guarded 24/7. The goal: to nearly eradicate the population of one species of mosquito, and with it, the heavy burden of malaria across Africa.
Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread
13623J. Min, C. Noble, D. Najjar and K. M. Esvelt, bioRxiv, 104877. 2017-02-06 13:30:21.
Here we describe a novel form of gene drive based on the introduction of multiple copies of an engineered ‘daisy’ sequence into repeated elements of the genome. Each introduced copy encodes guide RNAs that target one or more engineered loci carrying the CRISPR nuclease gene and the desired traits. When organisms encoding a drive system are released into the environment, each generation of mating with wild-type organisms will reduce the average number of the guide RNA elements per ‘daisyfield’ organism by half, serving as a generational clock
Gene Drives: A scientific case for a complete and perpetual ban
4597Latham, J, GeneWatch, 2017-02-06 00:00:00.
One of the central issues of our day is how to safely manage the outputs of industrial innovation. Novel products incorporating nanotechnology, biotechnology, rare metals, microwaves, novel chemicals, and more, enter the market on a daily basis. Yet none of these products come with an adequate data set of scientific information. Nor do they come with a clear intellectual framework within which their risks can be placed, as disputes over the precautionary principle show. The majority of products receive no regulatory supervision at all. How will the product be disposed of? What populations and which ecosystems will be exposed in the course of its advertised uses? What will be the consequences of accidental, off-label or illegal uses? Typically, none of these kinds of questions are adequately asked by government regulatory agencies unless citizens actively prod them to do so.; ; In consequence of these defects, we expose our world to unique hazards with every product launch. In comparison with its tremendous importance, this is surely one of the least discussed issues of our day.
Sterile Insect Techniques, GE mosquitoes and gene drives
4595Hanson, J, GeneWatch, 2017-02-06 00:00:00.
One of the great temptations in any field is to promote your solution to a problem as the only solution. The recent application of gene drives to sterilize mosquitoes that transmit malaria or viruses like dengue and zika is an example of this tendency to first develop a technology and then look for applications that might justify its use.; ; For at least 70 years, scientists have been trying to sterilize insects to prevent them from spreading disease, especially mosquito-borne diseases like malaria, dengue and zika, an approach known as "sterile insect technique." Sterilizing some insects with irradiation has been successful in preventing their reproduction.[1] In the 1950s, it was used to rid the southeastern U.S. of the New World screwworm Cochliomyia hominivorax (Coquerel), a deadly parasite of livestock. During the next 43 years the technique was used to eradicate this screwworm from the U.S., Mexico, and Central America. Currently, the largest use of Sterile Insect Technique in the U.S. is for the control of Mediterranean fruit fly. Irradiated bollworms are also being released to control cotton boll weevils, and irradiated coddling moths are being released to help protect apples and pears.[2] Interestingly, Rachel Carson, in Silent Spring, warned that using the Sterile Insect Technique to control a population of insects that could rebuild from neighboring islands or other populations was especially challenging. Talking about a SIT effort to control houseflies in the Florida Keys, she wrote:; ; "In a test on an island in the Florida Keys in 1961, a population of flies was nearly wiped out within a period of only five weeks. Repopulation of course followed from nearby islands, but as a pilot project the test was successful....; ; One of the problems of sterilization by radiation is that this requires not only artificial rearing but the release of sterile males in larger number than are present in the wild population. This could be done with the screw-worm, which is actually not an abundant insect. With the housefly, however, more than doubling the population through releases could be highly objectionable [to the local people]."[3]
How driving endonuclease genes can be used to combat pests and disease vectors
4043Godfray, HCJN, A.; Burt, A., BMC Biology, 15:81. 2017-01-21 00:00:00.
Driving endonuclease genes (DEGs) spread through a population by a non-Mendelian mechanism. In a heterozygote, the protein encoded by a DEG causes a double-strand break in the homologous chromosome opposite to where its gene is inserted and when the break is repaired using the homologue as a template the DEG heterozygote is converted to a homozygote. Some DEGs occur naturally while several classes of endonucleases can be engineered to spread in this way, with CRISPR-Cas9 based systems being particularly flexible. There is great interest in using driving endonuclease genes to impose a genetic load on insects that vector diseases or are economic pests to reduce their population density, or to introduce a beneficial gene such as one that might interrupt disease transmission. This paper reviews both the population genetics and population dynamics of DEGs. It summarises the theory that guides the design of DEG constructs intended to perform different functions. It also reviews the studies that have explored the likelihood of resistance to DEG phenotypes arising, and how this risk may be reduced. The review is intended for a general audience and mathematical details are kept to a minimum.
Is it time for synthetic biodiversity conservation?
4062Piaggio, AJS, G.; Seddon, P. J.; Alphey, L.; Bennett, E. L.; Carlson, R. H.; Friedman, R. M.; Kanavy, D.; Phelan, R.; Redford, K. H.; Rosales, M.; Slobodian, L.; Wheeler, K., Trends in Ecology & Evolution, 32:97-107. 2017-01-20 00:00:00.
Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.
Precaution: Open gene drive research
4042Esvelt, KM, Science, 355:589-590. 2017-01-20 00:00:00.
IN THEIR POLICY Forum “Precaution and governance of emerging technologies” (11 November 2016, p. 710), G. E. Kaebnick and colleagues convincingly assert that precaution is consistent with support for science. However, they overlook one way to improve safety while hastening discovery: Make research open.
Ethical implications of fighting malaria with CRISPR/Cas9
4061Patrão Neves, MD, Christiane, BMJ Global Health, 2:e000396. 2017-01-19 00:00:00.
Genome editing is a new, cheap and versatile technique which has great promise to combat vector-borne diseases. The current ethical debate worldwide is mainly concentrating on the dangers of germline intervention and less so on the potential for fighting vector-borne diseases. ; Gene drive technology has been significantly boosted by the CRISPR/Cas9 gene editing tool which may be able to combat malaria by targeting specific stretches of vector DNA and editing genomes at precise locations, working like a molecular scissors. However, CRISPR/Cas9 is currently not a ‘silver bullet’ and needs further research and consideration of the ethical aspects and consequences of its use.; In September 2016, the UNESCO Chair of Bioethics at the Medical University of Vienna convened a meeting entitled ‘Fighting Malaria with CRISPR/ Cas9: Ethical Implications’, which gathered together infectious disease experts with a focus on malaria, entomologists and ethicists to discuss the advantages and disadvantages of genome editing applied to mosquitoes to fight malaria. ; Although there was no formal consensus, some general conclusions were reached, in particular that any ethical debate needs to involve African stakeholders living in malaria areas and to consider future generations and the environment. The precautionary principle should be taken into account in any discussion, as should be the human cost of doing nothing.
Principles for gene drive research
4041Emerson, CJ, Stephanie; Littler, Katherine; Randazzo, Filippo, Science, 358:1135. 2017-01-19 00:00:00.
The recent outbreak of Zika virus in the Americas renewed attention on the importance of vector-control strategies to fight the many vector-borne diseases that continue to inflict suffering around the world. In 2015, there were ?212 million infections and a death every minute from malaria alone (1). Gene drive technology is being explored as a potentially durable and cost-effective strategy for controlling the transmission of deadly and debilitating vector-borne diseases that affect millions of people worldwide, such as Zika virus and malaria. Additionally, its suitability is being evaluated for various potential applications in conservation biology, including a highly specific and humane method for eliminating invasive species from sensitive ecosystems (2, 3).
Conditions for success of engineered underdominance gene drive systems
4040Edgington, MPA, L. S., Journal of Theoretical Biology, 430:128-140. 2017-01-18 00:00:00.
Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens.
Evolutionary dynamics of CRISPR gene drives
4059Noble, CO, Jason; Esvelt, Kevin M.; Church, George M.; Nowak, Martin A., Science Advances, 3:e1601964. 2017-01-17 00:00:00.
The alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, clustered regularly interspaced short palindromic repeats (CRISPR) gene drives—selfish genetic elements that can spread through populations even if they confer no advantage to their host organism—are rapidly emerging as the most promising approach. However, before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design that selects against resistant alleles could greatly improve evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights that inform the engineering of practical gene drive systems.%U
Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics
4039Eckhoff, PAW, E. A.; Godfray, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 114:e255-e264. 2017-01-17 00:00:00.
The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings.
CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations
4038Drury, DWD, A. L.; Siniard, D. J.; Zentner, G. E.; Wade, M. J., Science Advances, 3:e1601910. 2017-01-16 00:00:00.
Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.
Engineering species-like barriers to sexual reproduction
4057Maselko, MH, Stephen C.; Chacón, Jeremy M.; Harcombe, William R.; Smanski, Michael J., Nature Communications, 8:883. 2017-01-15 00:00:00.
Controlling the exchange of genetic information between sexually reproducing populations has applications in agriculture, eradication of disease vectors, control of invasive species, and the safe study of emerging biotechnology applications. Here we introduce an approach to engineer a genetic barrier to sexual reproduction between otherwise compatible populations. Programmable transcription factors drive lethal gene expression in hybrid offspring following undesired mating events. As a proof of concept, we target the ACT1 promoter of the model organism Saccharomyces cerevisiae using a dCas9-based transcriptional activator. Lethal overexpression of actin results from mating this engineered strain with a strain containing the wild-type ACT1 promoter.
The promise and peril of CRISPR gene drives
4076Zentner, GEW, Michael J. C., Bioessays, 39:1-9. 2017-01-14 00:00:00.
Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives.
A bigger toolbox: Biotechnology in biodiversity conservation
6012R. T. Corlett, Trends in Biotechnology, 35:55-65. 2017-01-13 20:08:47.
Conservation biology needs a bigger toolbox to meet unprecedented challenges. Genomics, fueled by declining sequencing costs, offers novel tools with increased precision for genetic questions previously answered with a few molecular markers, as well as completely new possibilities. Metabarcoding promises quicker, cheaper, and more accurate assessments of biodiversity in groups that are difficult to assess by traditional methods, while sequencing low-quality DNA extends the range of useable materials to include museum specimens, archeological remains, and environmental samples. Genomic and transcriptomic data can be used to assess the potential of populations to adapt to new challenges. In the near future, gene-editing tools may help endangered species cope with change, while gene drives control unwanted species and help wanted ones. De-extinction has become a serious prospect.
Agricultural pest control with CRISPR-based gene drive: time for public debate: Should we use gene drive for pest control?
4035Courtier?Orgogozo, VM, Baptiste; Boëte, Christophe, EMBO Reports, 18:878-880. 2017-01-13 00:00:00.
Gene drive based on the CRISPR/Cas-9 gene editing system is a powerful technology that promotes the inheritance of the gene drive tool itself via sexual reproduction and can therefore spread quickly through a population. It holds great potential for public health and humanitarian purposes, such as reducing the burden of vector-borne diseases like malaria. Here, we discuss another potential application of CRISPR-based gene drive, namely the control of pest species to increase crop production. We argue that gene drive-based pest control strategies should receive more attention from policymakers and the public given their enormous potential impact on the environment, their easy accessibility, and the current dearth of regulations.
Introduction of a male-harming mitochondrial haplotype via ‘Trojan Females’ achieves population suppression in fruit flies
4074Wolff, JNG, N. J.; Tompkins, D. M.; Dowling, D. K., eLife, 6:e23551. 2017-01-12 00:00:00.
Pests are a global threat to biodiversity, ecosystem function, and human health. Pest control approaches are thus numerous, but their implementation costly, damaging to non-target species, and ineffective at low population densities. The Trojan Female Technique (TFT) is a prospective self-perpetuating control technique that is species-specific and predicted to be effective at low densities. The goal of the TFT is to harness naturally occurring mutations in the mitochondrial genome that impair male fertility while having no effect on females. Here, we provide proof-of-concept for the TFT, by showing that introduction of a male fertility-impairing mtDNA haplotype into replicated populations of Drosophila melanogaster causes numerical population suppression, with the magnitude of effect positively correlated with its frequency at trial inception. Further development of the TFT could lead to establishing a control strategy that overcomes limitations of conventional approaches, with broad applicability to invertebrate and vertebrate species, to control environmental and economic pests.
Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations
4034Champer, JR, Riona; Oh, Suh Yeon; Liu, Chen; Liu, Jingxian; Clark, Andrew G.; Messer, Philipp W., PLOS Genetics, 13:e1006796. 2017-01-12 00:00:00.
Author summary Gene drive systems provide a wide array of potential applications, including new strategies for the control of vector-borne diseases. For example, a functioning gene drive system could rapidly spread a genetically modified allele designed to reduce pathogen transmission throughout a vector population. The recently developed CRISPR/Cas9-based gene drive mechanism works by converting wild type alleles to drive alleles in heterozygotes via cleavage and homology-directed repair. However, resistance alleles that are unable to be converted to drive alleles can also be generated during this process, which may pose a major obstacle to the practical use of such gene drives. In our study, we developed two CRISPR/Cas9 gene drive constructs using different promoters and target sites in the model organism Drosophila melanogaster. We observed that these constructs produced resistance alleles at high rates both in the germline and post-fertilization in the embryo. Additionally, conversion efficiency and resistance allele formation rates varied substantially among genetically diverse fly lines. Overall, we conclude that new gene drive approaches will be necessary to reduce the formation of resistance alleles, particularly in genetically diverse natural populations.
A transatlantic perspective on 20 emerging issues in biological engineering
4073Wintle, BCB, C. R.; Rhodes, C.; Molloy, J. C.; Millett, P.; Adam, L.; Breitling, R.; Carlson, R.; Casagrande, R.; Dando, M.; Doubleday, R.; Drexler, E.; Edwards, B.; Ellis, T.; Evans, N. G.; Hammond, R.; Haseloff, J.; Kahl, L.; Kuiken, T.; Lichman, B. R.; Matthewman, C. A.; Napier, J. A.; OhEigeartaigh, S. S.; Patron, N. J.; Perello, E.; Shapira, P.; Tait, J.; Takano, E.; Sutherland, W. J., eLife, 6:21. 2017-01-11 00:00:00.
Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.
Gene Drive 101: A Basic Guidance Resource for Biosafety Professionals
4053Krishnan, PG, David, Applied Biosafety, 22:181-184. 2017-01-11 00:00:00.
Biosafety risk assessment and containment framework strategies for research involving gene drives pose a challenge, as there are no published guidelines or regulatory information yet written specifically addressing biosafety and gene drive use. Since the risk is more at an ecologic population level than an individual risk to the researcher, this further confounds the typical risk assessment process, which traditionally places emphasis on evaluating biosafety risks to the user and how the agent is spread among permissible hosts. We also realize that many of the publications currently available for gene drive biosafety are written with the assumption that readers have a good grasp of molecular biology and genetics. We have good reason to believe that this assumption is neither correct nor justified among all biosafety professionals. Our goal here is to create a resource that would offer a basic primer on gene drive technology while providing enough resources to start the risk assessment process of a gene drive proposal. We developed several questions and answers that we believe will make tackling the biosafety aspects of a gene proposal less formidable.
Teilhard de Chardin’s oeuvre within an ongoing discussion of a gene drive release for public health reasons
4033Cartolovni, A, Life Sciences, Society and Policy, 13:18. 2017-01-11 00:00:00.
Within the domain of public health, vector-borne diseases are among the most vehemently discussed issues. Recent scientific breakthroughs in genome editing technology provided a solution to this issue in the form of a gene drive that might decrease and even eradicate vector-borne diseases. Gene drives are engineered, and designed genes that can break typical inheritance rules and be passed to almost all of the carrier’s offspring. This genome editing and gene drive technology has become a powerful tool for ecological and environmental engineering, through which man can manipulate his surroundings, adjusting it to himself and directly mastering evolution and the ecosystem. Although the gene drive technology has been perceived as promising in the public health domain, ecological implications of its use are not to be underestimated. The primary aim of this paper is to overcome the ongoing discussion which mostly focuses on whether priority should be given to the environment or to public health, and to find an adequate answer and solution. In this quest to find the proper answer and solution, Pierre Teilhard de Chardin’s thought might be useful, especially his concepts of the biosphere and the noosphere which may provide some clarifications as to why we are at the moment so cautious with gene drive technology and how we need to move towards a better common future on earth.
Recommendations for Laboratory Containment and Management of Gene Drive Systems in Arthropods
4032Benedict, MQB, Austin; Capurro, Margareth L.; De Barro, Paul; Handler, Alfred M.; Hayes, Keith R.; Marshall, John M.; Tabachnick, Walter J.; Adelman, Zach N., Vector-Borne and Zoonotic Diseases, 18:2-13. 2017-01-10 00:00:00.
Versatile molecular tools for creating driving transgenes and other invasive genetic factors present regulatory, ethical, and environmental challenges that should be addressed to ensure their safe use. In this article, we discuss driving transgenes and invasive genetic factors that can potentially spread after their introduction into a small proportion of individuals in a population. The potential of invasive genetic factors to increase their number in natural populations presents challenges that require additional safety measures not provided by previous recommendations regarding accidental release of arthropods. In addition to providing physical containment, invasive genetic factors require greater attention to strain management, including their distribution and identity confirmation. In this study, we focus on insects containing such factors with recommendations for investigators who are creating them, institutional biosafety committees charged with ensuring safety, funding agencies providing support, those managing insectaries handling these materials who are responsible for containment, and other persons who will be receiving insects?transgenic or not?from these facilities. We give specific examples of efforts to modify mosquitoes for mosquito-borne disease control, but similar considerations are relevant to other arthropods that are important to human health, the environment, and agriculture.; Versatile molecular tools for creating driving transgenes and other invasive genetic factors present regulatory, ethical, and environmental challenges that should be addressed to ensure their safe use. In this article, we discuss driving transgenes and invasive genetic factors that can potentially spread after their introduction into a small proportion of individuals in a population. The potential of invasive genetic factors to increase their number in natural populations presents challenges that require additional safety measures not provided by previous recommendations regarding accidental release of arthropods. In addition to providing physical containment, invasive genetic factors require greater attention to strain management, including their distribution and identity confirmation. In this study, we focus on insects containing such factors with recommendations for investigators who are creating them, institutional biosafety committees charged with ensuring safety, funding agencies providing support, those managing insectaries handling these materials who are responsible for containment, and other persons who will be receiving insects?transgenic or not?from these facilities. We give specific examples of efforts to modify mosquitoes for mosquito-borne disease control, but similar considerations are relevant to other arthropods that are important to human health, the environment, and agriculture.
Evaluating strategies for reversing CRISPR-Cas9 gene drives
4071Vella, MRG, Christian E.; Lloyd, Alun L.; Gould, Fred, Scientific Reports, 7:11038. 2017-01-09 00:00:00.
A gene drive biases inheritance of a gene so that it increases in frequency within a population even when the gene confers no fitness benefit. There has been renewed interest in environmental releases of engineered gene drives due to recent proof of principle experiments with the CRISPR-Cas9 system as a drive mechanism. Release of modified organisms, however, is controversial, especially when the drive mechanism could theoretically alter all individuals of a species. Thus, it is desirable to have countermeasures to reverse a drive if a problem arises. Several genetic mechanisms for limiting or eliminating gene drives have been proposed and/or developed, including synthetic resistance, reversal drives, and immunizing reversal drives. While predictions about efficacy of these mechanisms have been optimistic, we lack detailed analyses of their expected dynamics. We develop a discrete time model for population genetics of a drive and proposed genetic countermeasures. Efficacy of drive reversal varies between countermeasures. For some parameter values, the model predicts unexpected behavior including polymorphic equilibria and oscillatory dynamics. The timing and number of released individuals containing a genetic countermeasure can substantially impact outcomes. The choice among countermeasures by researchers and regulators will depend on specific goals and population parameters of target populations.
Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing
4031Beaghton, AH, Andrew; Nolan, Tony; Crisanti, Andrea; Godfray, H. Charles J.; Burt, Austin, Genetics, 205:1587-1596. 2017-01-09 00:00:00.
There is a need for new interventions against the ongoing burden of vector-borne diseases such as malaria and dengue. One suggestion has been to develop genes encoding effector molecules that block parasite development within the vector, and then use the nuclease-based homing reaction as a form of gene drive to spread those genes through target populations. If the effector gene reduces the fitness of the mosquito and does not contribute to the drive, then loss-of-function mutations in the effector will eventually replace functional copies, but protection may nonetheless persist sufficiently long to provide a public health benefit. Here, we present a quantitative model allowing one to predict the duration of protection as a function of the probabilities of different molecular processes during the homing reaction, various fitness effects, and the efficacy of the effector in blocking transmission. Factors that increase the duration of protection include reducing the frequency of pre-existing resistant alleles, the probability of nonrecombinational DNA repair, the probability of homing-associated loss of the effector, the fitness costs of the nuclease and effector, and the completeness of parasite blocking. For target species that extend over an area much larger than the typical dispersal distance, the duration of protection is expected to be highest at the release site, and decrease away from there, eventually falling to zero, as effector-less drive constructs replace effector-containing ones. We also model an alternative strategy of using the nuclease to target an essential gene, and then linking the effector to a sequence that restores the essential function and is resistant to the nuclease. Depending upon parameter values, this approach can prolong the duration of protection. Our models highlight the key design criteria needed to achieve a desired level of public health benefit.%U http://www.genetics.org/content/genetics/205/4/1587.full.pdf
Sry gene drive for rodent control: Reply to Gemmell and Tompkins
4051Kanavy, DS, M., Trends in Ecology & Evolution, 32:315-316. 2017-01-09 00:00:00.
We would like to thank Gemmell and Tompkins for their interest and comments onthe articlebyPiaggioet al. [1].Theissues raised by Gemmell and Tompkins [2] are very pertinent, and they correctly identified that the format of the article did not lend itself to a comprehensive discussion of the ideas of using gene drives in mice. The method being considered in the Piaggio et al. article is to utilize a naturally occurring t-allele transgene (Tg) to sex-bias amouse population, causing it to crash. Inserting the sex-determining region on the Y chromosome (Sry) into the Tg allows biased inheritance where the majority of the offspring born are phenotypically male.
Eradicating Mosquitoes? The promise and peril of gene drive technologies.
4050Jun, B-O, Eubios Journal of Asian and International Bioethics, 27:113-116. 2017-01-08 00:00:00.
This paper discusses the ethical issues associated with genetic modification of mosquito species that are human disease vectors. The Oxitec genetically changed mosquito—a variant of a species called Aedes aegypti, OX513A, is taken as an example. The benefits and risks are discussed, and questions need to be discussed in public prior to release of this gene drive system
Evolution of Resistance Against CRISPR/Cas9 Gene Drive
4070Unckless, RLC, A. G.; Messer, P. W., Genetics, 205:827-841. 2017-01-08 00:00:00.
CRISPR/Cas9 gene drive (CGD) promises to be a highly adaptable approach for spreading genetically engineered alleles throughout a species, even if those alleles impair reproductive success. CGD has been shown to be effective in laboratory crosses of insects, yet it remains unclear to what extent potential resistance mechanisms will affect the dynamics of this process in large natural populations. Here we develop a comprehensive population genetic framework for modeling CGD dynamics, which incorporates potential resistance mechanisms as well as random genetic drift. Using this framework, we calculate the probability that resistance against CGD evolves from standing genetic variation, de novo mutation of wild-type alleles, or cleavage repair by nonhomologous end joining (NHEJ)-a likely by-product of CGD itself. We show that resistance to standard CGD approaches should evolve almost inevitably in most natural populations, unless repair of CGD-induced cleavage via NHEJ can be effectively suppressed, or resistance costs are on par with those of the driver. The key factor determining the probability that resistance evolves is the overall rate at which resistance alleles arise at the population level by mutation or NHEJ. By contrast, the conversion efficiency of the driver, its fitness cost, and its introduction frequency have only minor impact. Our results shed light on strategies that could facilitate the engineering of drivers with lower resistance potential, and motivate the possibility to embrace resistance as a possible mechanism for controlling a CGD approach. This study highlights the need for careful modeling of the population dynamics of CGD prior to the actual release of a driver construct into the wild.
Vector control with driving Y chromosomes: modelling the evolution of resistance
4030Beaghton, AB, P. J.; Burt, A., Malaria Journal, 16:286. 2017-01-08 00:00:00.
: The introduction of new malaria control interventions has often led to the evolution of resistance, both of the parasite to new drugs and of the mosquito vector to new insecticides, compromising the efficacy of the interventions. Recent progress in molecular and population biology raises the possibility of new genetic-based interventions, and the potential for resistance to evolve against these should be considered. Here, population modelling is used to determine the main factors affecting the likelihood that resistance will evolve against a synthetic, nuclease-based driving Y chromosome that produces a male-biased sex ratio. Methods: A combination of deterministic differential equation models and stochastic analyses involving branching processes and Gillespie simulations is utilized to assess the probability that resistance evolves against a driving Y that otherwise is strong enough to eliminate the target population. The model considers resistance due to changes at the target site such that they are no longer cleaved by the nuclease, and due to trans-acting autosomal suppressor alleles. Results: The probability that resistance evolves increases with the mutation rate and the intrinsic rate of increase of the population, and decreases with the strength of drive and any pleiotropic fitness costs of the resistant allele. In seasonally varying environments, the time of release can also affect the probability of resistance evolving. Trans-acting suppressor alleles are more likely to suffer stochastic loss at low frequencies than target site resistant alleles. Conclusions: As with any other intervention, there is a risk that resistance will evolve to new genetic approaches to vector control, and steps should be taken to minimize this probability. Two design features that should help in this regard are to reduce the rate at which resistant mutations arise, and to target sequences such that if they do arise, they impose a significant fitness cost on the mosquito.
New Weapons in the Toad Toolkit: A Review of Methods to Control and Mitigate the Biodiversity Impacts of Invasive Cane Toads (Rhinella Marina)
4069Tingley, RW-F, Georgia; Schwarzkopf, Lin; Greenlees, Matthew J.; Phillips, Benjamin L.; Brown, Gregory; Clulow, Simon; Webb, Jonathan; Capon, Robert; Sheppard, Andy; Strive, Tanja; Tizard, Mark; Shine, Richard, The Quarterly Review of Biology, 92:123-149. 2017-01-07 00:00:00.
Our best hope of developing innovative methods to combat invasive species is likely to come from the study of high-profile invaders that have attracted intensive research not only into control, but also basic biology. Here we illustrate that point by reviewing current thinking about novel ways to control one of the world?s most well-studied invasions: that of the cane toad in Australia. Recently developed methods for population suppression include more effective traps based on the toad?s acoustic and pheromonal biology. New tools for containing spread include surveillance technologies (e.g., eDNA sampling and automated call detectors), as well as landscape-level barriers that exploit the toad?s vulnerability to desiccation?a strategy that could be significantly enhanced through the introduction of sedentary, range-core genotypes ahead of the invasion front. New methods to reduce the ecological impacts of toads include conditioned taste aversion in free-ranging predators, gene banking, and targeted gene flow. Lastly, recent advances in gene editing and gene drive technology hold the promise of modifying toad phenotypes in ways that may facilitate control or buffer impact. Synergies between these approaches hold great promise for novel and more effective means to combat the toad invasion and its consequent impacts on biodiversity.
Spatial gene drives and pushed genetic waves
4068Tanaka, HS, Howard A.; Nelson, David R., Proceedings of the National Academy of Sciences of the United States of America, 114:8452. 2017-01-06 00:00:00.
Gene constructs introduced into natural environments have been proposed to solve various ecological problems. The CRISPR-Cas9 technology greatly facilitates construction of gene drives that allow desired traits to rapidly replace wild types, even if these convey a selective growth rate disadvantage s > 0. However, accidental release of a gene drive could damage ecosystems irreversibly. We have modeled the spatial spread of gene drives and find a preferred range of selective disadvantages, 0.5 < s < 0.697. In this regime, gene drives spread but only when a nucleus exceeds a critical size and intensity. By making gene drives uniquely susceptible to a compound, their advance can be stopped in two dimensions by finite-width barriers, even when interrupted by gaps.Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction–diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage s > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < s < 0.697, a rather narrow range. In this “pushed wave” regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called “critical propagule,” which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable (“sensitizing drive”) in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps.
Towards the genetic control of invasive species
4047Harvey-Samuel, TA, T.; Alphey, L., Biological Invasions, 19:1683-1703. 2017-01-05 00:00:00.
Invasive species remain one of the greatest threats to global biodiversity. Their control would be enhanced through the development of more effective and sustainable pest management strategies. Recently, a novel form of genetic pest management (GPM) has been developed in which the mating behaviour of insect pests is exploited to introduce genetically engineered DNA sequences into wild conspecific populations. These 'transgenes' work in one or more ways to reduce the damage caused by a particular pest, for example reducing its density, or its ability to vector disease. Although currently being developed for use against economically important insect pests, these technologies would be highly appropriate for application against invasive species that threaten biodiversity. Importantly, these technologies have begun to advance in scope beyond insects to vertebrates, which include some of the world's worst invasives. Here we review the current state of this rapidly progressing field and, using an established set of eradication criteria, discuss the characteristics which make GPM technologies suitable for application against invasive pests.
Results from the Workshop “Problem Formulation for the Use of Gene Drive in Mosquitoes”
4066Roberts, ADA, P. P.; Okumu, F.; Quemada, H.; Savadogo, M.; Singh, J. A.; James, S., American Journal of Tropical Medicine and Hygiene, 96:530-533. 2017-01-04 00:00:00.
Reducing the incidence of malaria has been a public health priority for nearly a century. New technologies and associated vector control strategies play an important role in the prospect of sustained reductions. The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene-drive constructs to reduce or alter vector populations to reduce malaria incidence. However, before these technologies can be developed and exploited, it will be necessary to understand and assess the likelihood of any potential harms to humans or the environment. To begin this process, the Foundation for the National Institutes of Health and the International Life Sciences Institute Research Foundation organized an expert workshop to consider the potential risks related to the use of gene drives in Anopheles gambiae for malaria control in Africa. The resulting discussion yielded a series of consensus points that are reported here.
The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
4046Hammond, AMK, Kyros; Bruttini, Marco; North, Ace; Galizi, Roberto; Karlsson, Xenia; Kranjc, Nace; Carpi, Francesco M.; D’Aurizio, Romina; Crisanti, Andrea; Nolan, Tony, PLOS Genetics, 13:e1007039. 2017-01-04 00:00:00.
Gene drives are selfish genetic elements that are able to bias their own inheritance among offspring. Starting from very low frequencies they can rapidly invade a population in just a few generations, even when imposing a fitness cost. Gene drives based on the precise DNA cutting enzyme CRISPR have been shown recently to be highly efficient at copying themselves from one chromosome to the other during the process of gamete formation in mosquitoes, resulting in transmission to 99% of offspring instead of the 50% expected for a single gene copy. One proposed use for CRISPR-based gene drives is in the control of mosquitoes by designing the gene drive to target mosquito genes involved in fertility, thereby reducing their overall reproductive output and leading to population suppression. Like any intervention designed to suppress a population these gene drives are expected to select for mutations in the mosquito that are resistant to the drive and restore fertility to mosquitoes. We have analyzed the origin and selection of resistant alleles in caged populations of mosquitoes initiated with a gene drive construct targeting a female fertility gene. We find the selected alleles are in-frame insertions and deletions that are resistant to cleavage and restore female fertility. Our findings allow us to improve predictions on gene drive behaviour and to make concrete recommendations on how to improve future gene drive designs by decreasing the likelihood that they generate resistance.
Advances in vector control science: Rear-and-release strategies show promise… but don’t forget the basics
4065Ritchie, SAJ, B. J., Journal of Infectious Diseases, 215:S103-S108. 2017-01-03 00:00:00.
Both chikungunya and Zika viruses have recently swept from Africa across the Pacific to the Americas, causing major outbreaks of disease in humans. In the meantime, dengue epidemics continue throughout the tropics. Traditional vector control programs based on strategies from 1950s and 1960s have been relatively ineffective in combating recent epidemics. In response, new methods involving the rearing and releasing of large numbers of mosquitoes to eliminate or modify local Aedes populations are being developed, with several currently conducting field releases in high-risk countries. These advances, include the release of Wolbachia-infected Aedes aegypti and Aedes albopictus, for either its virus-blocking capabilities, sterilization by cytoplasmic incompatibility, or both; the release of Aedes carrying dominant lethal genes, such as the OX513A strain of A. aegypti; and other emerging techniques, such as advancing gene-drive technologies, are summarized, as well as current stages of development and primary operational and regulatory hurdles. Although these technologies show great promise, none are ready for widespread rollout for cities of millions of people. Thus, efforts should be made to avoid methods such as space sprays that have failed and improve existing technologies to increase their efficacy.
CRISPR-based gene drive in agriculture will face technical and governance challenges
4045Gutzmann, NE, Johanna E.; Barnes, Jessica Cavin; Baltzegar, Jennifer; Jones, Michael S.; Sudweeks, Jayce, EMBO reports, 18:1479-1480. 2017-01-03 00:00:00.
Comment on "Agricultural pest control with CRISPR-based gene drive: time for public debate" by Courtier-Orgogozo et al.
CRISPR/Cas9 gene drive: Growing pains for a new technology
4064Reed, FA, Genetics, 205:1037-1039. 2017-01-02 00:00:00.
In this commentary, Floyd Reed discusses Unckless et al. (2017),; “Evolution of resistance against CRISPR/Cas9 gene drive,”; which was published in the February issue of GENETICS.
Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
4044Gonen, SJ, J.; Gorjanc, G.; Mileham, A. J.; Whitelaw, C. B. A.; Hickey, J. M., Genetics Selection Evolution, 49:14. 2017-01-02 00:00:00.
This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. Methods: We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance (sigma(2)(A)), rate of change in inbreeding (Delta F), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Results: Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Conclusions: Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding.
The End of the GMO? Genome Editing, Gene Drives and New Frontiers of Plant Technology
15368K. L. Hefferon and R. J. Herring, Review of Agrarian Studies, 7. 2017-01-01 21:40:33.
mprovements to agriculture will constitute one of the world’s greatest challenges in the coming century. Political and social controversies, as well as complications of plant breeding, intellectual property, and regulation, have compromised the promised impact of genetically engineered – typically transgenic – crops designated as “GMOs.” Genome editing is a new suite of molecular tools for assisting biologists identify genes that control agronomic traits such as drought tolerance and pest resistance, as well as to elucidate how expression of these genes is intertwined within the functional framework of the cell. This technology has recently gained momentum for its ability to accelerate the crop breeding process in an unprecedented fashion and expand the range of crop varieties with improved precision and lower costs. This review explains the basic concepts and provides examples of how genome editing could help address the United Nation’s Sustainable Development Goals with respect to food, agriculture, and medicine. It concludes with a discussion of the potential social impact of genome editing and gene drive. These effects are contingent on the resolution of novel ethical and regulatory challenges that add new layers of complexity to societal questions of appropriate technology, in agriculture and beyond. We expect these questions to replace the irresolvable GMO debate.
Driving out malaria
4598Nolan, TC, A., Scientist, 2017-01-01 00:00:00.
In recent years, researchers have sequenced the genomes of several Anopheles mosquito species, including those responsible for nearly all of the malaria transmission in Africa. With this information, they have begun to identify the genes underlying the insects’ ability to colonize human habitats, their reproductive biology, and their susceptibility to infection by the malaria parasite (Plasmodium spp.). If we know the genes, or variants of genes, that are responsible for key mosquito traits, such as parasite clearance or egg laying, we can theoretically introduce a genetic modification into the insects that reduces malaria transmission.
Gene drive and collective oversight
4594Esvelt, K, GeneWatch, 2017-01-01 00:00:00.
As one of the scientists who first described how CRISPR could create gene drive systems capable of altering wild; populations, I am morally responsible for the consequences. I'm writing to you in the hope that the people most; critical of the very idea can help. Bluntly, gene drive is an example of how the current scientific enterprise causes; our technological power to grow faster than our ability to ensure it is developed wisely. But because it affects the; shared environment, gene drive may also be the key to improving the system - namely, by causing it to favor; collective oversight. And to do that, we need your help.
Concept and history of genetic control
6014Scott, M. J. and Benedict, M. Q., Genetic Control of Malaria and Dengue, 2:31-54. 2016-12-30 20:16:45.
Genetic control of insects is an established method, mainly for insects that are important crop and veterinary pests such as medflies and screwworm. Efforts to use the same technologies against insects of medical importance, especially mosquitoes, have had limited success. The successes against mosquitoes have been accomplished using forms of both conventional and modern methods, both of which are promising. In this chapter, we provide highlights of the development of genetic control of agricultural pests and describe how the development of methods against mosquitoes reflects those advances. While admiring successful genetic control programs is motivating, we suggest that much can also be learned from both past successful and failed efforts, as doing so will increase our ability to improve future activities.
The Case for a Global Moratorium on Genetically-engineered Gene Drives
4602Civil Society Working Group on Gene Drives, SynBioWatch, 2016-12-05 00:00:00.
In view of the significant ecological, cultural and societal threats posed by genetically-engineered gene drives, including threats to biodiversity, national sovereignty, peace and food security, we the undersigned call upon governments at the 13th Conference of the Parties to the Convention on Biological Diversity, in accordance with the precautionary principle, to put in place a moratorium on 1) any further technical development and experimental application of gene drives, and 2) environmental release of genetically-engineered gene drives.
Invertebrate Biosecurity Challenges in High-Productivity Grassland: The New Zealand Example
13738S. L. Goldson, B. I. P. Barratt and K. F. Armstrong, Frontiers in Plant Science, 7. 2016-11-15 19:35:24.
This review explores the unique challenges faced by pasture biosecurity and what may be done to confront existing difficulties. While there is no silver bullet, and limited opportunity pre and at for improving pasture biosecurity, advancement may include increased and informed vigilance by farmers, pheromone traps and resistant plants to slow invasion. Increasingly, there is also the potential for more use of improved population dispersal models and surveillance strategies including unmanned aerial vehicles, as well as emerging techniques to determine invasive pest genomes and their geographical origins.
Guidance on risk assessment of living modified organisms and monitoring in the context of risk assessment
16062Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment and Risk Management,, Convention on Biological Diversity, 2016-09-14 21:27:35.
This document was developed by the Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment and Risk Management, with input from the Open-ended Online Expert Forum, in accordance with terms of reference set out by the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety (COP-MOP) in its decisions BS-IV/11 and BSV/12 in response to an identified need for further guidance on risk assessment of LMOs. 4 It is intended to be a “living document” that may be updated and improved as appropriate and when mandated by the Parties to the Cartagena Protocol on Biosafety.
Biodiversity, GMOs, Gene Drives and the Militarised Mind
4605Shiva, V, Inter Press Service, 2016-07-18 00:00:00.
A recent report from the National Academy of Science of The United States, titled Gene Drives on the Horizon : Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values”, warns:; “One possible goal of release of a gene-drive modified organism is to cause the extinction of the target species or a drastic reduction in its abundance.”; Gene Drives have been called “mutagenic chain reactions”, and are to the biological world what chain reactions are to the nuclear world. The Guardian describes Gene Drives as the “gene bomb”.
Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values
6356U. S. National Academies of Sciences, Engineering, and Medicine, The National Academies Press, 2016-07-08 20:32:51.
Scientists have studied gene drives for more than 50 years. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussion of the potential applications and implications of gene drive technologies. Just prior to the beginning of this study and since the committee was first convened, scientists published four proofs of concept— one in yeast, one in fruit flies, and two in different species of mosquitoes—that demonstrate the successful development of gene drives in the laboratory, at least in these organisms. Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as gene editing tools become more refined. Gene-drive modified organisms are on the horizon. The fast moving nature of this field is both encouraging and concerning. While gene-drive modified organisms hold promise for addressing difficult to solve, persistent challenges, such as the eradication of vector-borne diseases and the conservation of threatened and endangered species, these proposed applications are based on limited proof-of-concept studies. The presumed efficiency of gene-drive modified organisms may lead to calls for their release in perceived crisis situations, before there is adequate knowledge of their ecological effects, and before mitigation plans for unintended harmful consequences are in place. Responding to this fast moving field, the National Institutes of Health (NIH) and the Foundation for the National Institutes of Health (FNIH)2 asked the National Academies of Sciences, Engineering, and Medicine to convene a committee with a broad range of expertise to summarize the scientific discoveries related to gene drives and considerations for their responsible use. Proof-of-concept in a few laboratory studies is not sufficient in and of itself to support a decision to release gene-drive modified organisms into the environment. Laboratory and field research is needed to refine CRISPR/Cas9-based gene drives and other gene drive mechanisms, and to understand how gene drives might work under different environmental conditions and in a wide variety of organisms. The considerable gaps in knowledge about potential off-target (within the organism) and non-target (in other species or the environment) effects necessitate a collaborative, multidisciplinary approach to research, ecological risk assessment, development of public policy, and decision making for each proposed application of a gene drive technology. General principles to guide responsible practices for gene drives from the laboratory setting through to field release and monitoring are embedded as recommendations throughout the report.
Gene Drives: Saving Lives Or Powering Extinctions?
5491Fw:Thinking, 2016-07-06 18:25:32.
A few months back we talked about the revolutionary gene-editing technique known as CRISPR-Cas9 – a technology based on the bacterial immune system that will allow us to make edits to an organism’s genetic code with more ease and accuracy than ever before. CRISPR is changing the landscape of genetic engineering and synthetic biology. In this episode, we take a look at one of the most powerful applications in this new landscape of genetic engineering: Gene drives. This is an idea that has the potential to save millions of lives and give us unprecedented control over natural populations of organisms. At the same time, it comes with serious risks that need to be studied and understood. Should we use gene drives at all? If so, what should we use them for? And what safety measures should we put in place?
Gene Drive Technology: Where is the Future?
6904National Academy of Sciences Engineering Medicine, BioScience Talks, 2016-06-29 14:38:31.
Gene drives have the potential to revolutionize approaches to major public health, conservation, and agricultural problems. For instance, gene drives might one day prevent mosquitoes from spreading a variety of deadly diseases, including Zika virus, malaria, and others. A form of genetic modification, the technology works by causing a particular genetic element to spread through populations, thereby making it possible to change species in the wild. Despite the significant promise, caution is warranted, says a new report from the National Academies of Sciences, Engineering, and Medicine's Committee on Gene Drive Research. According to the committee, gene drives raise a variety of ecological and regulatory questions that have yet to be answered. For this episode of BioScience Talks, we're joined by committee co-chair Dr. James P. Collins of Arizona State University and committee member Dr. Joseph Travis of Florida State University. They fill us in on the specifics of the report and on the future of gene drives.
Openly Engineering Our Ecosystems
5479TEDxCambridge, 2016-06-22 18:00:37.
Which technologies should we develop and how? Kevin Esvelt, leader of the Sculpting Evolution group and a professor at the MIT Media Lab, describes how CRISPR 'gene drives' can single-handedly alter entire wild populations and the critical importance of requiring powerful technologies to be developed in the open light of day.
Prospects and challenges of CRISPR/Cas genome editing for the study and control of neglected vector-borne nematode diseases
6017M. Zamanian and E. C. Andersen, The FEBS Journal, 283:3204-3221. 2016-06-14 20:22:18.
Neglected tropical diseases caused by parasitic nematodes inflict an immense health and socioeconomic burden throughout much of the developing world. Current estimates indicate that more than two billion people are infected with nematodes, resulting in the loss of 14 million disability-adjusted life years per annum. Although these parasites cause significant mortality, they primarily cause chronic morbidity through a wide range of severe clinical ailments. Treatment options for nematode infections are restricted to a small number of anthelmintic drugs, and the rapid expansion of anthelmintic mass drug administration raises concerns of drug resistance. Preservation of existing drugs is necessary, as well as the development of new treatment options and methods of control. We focus this review on how the democratization of CRISPR/Cas9 genome editing technology can be enlisted to improve our understanding of the biology of nematode parasites and our ability to treat the infections they cause. We will first explore how this robust method of genome manipulation can be used to newly exploit the powerful model nematode Caenorhabditis elegans for parasitology research. We will then discuss potential avenues to develop CRISPR/Cas9 editing protocols in filarial nematodes. Lastly, we will propose potential ways in which CRISPR/Cas9 can be used to engineer gene drives that target the transmission of mosquito-borne filarial nematodes.
Lethal Gene Drive Selects Inbreeding
13627J. J. Bull, bioRxiv, 046847. 2016-06-03 13:55:41.
ere, population genetic models are used to consider the evolution of inbreeding (specifically selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical analyses indicate a rich set of outcomes, but selfing often evolves in response to the HEG, with a corresponding partial restoration of mean fitness. Whether selfing does indeed evolve and its effect in restoring fitness depends heavily on the magnitude of inbreeding depression. Overall, these results point toward an underappreciated evolutionary response to block the harmful effects of a selfish gene.
Gene editing can now change an entire species — forever
5495TED, 2016-06-02 18:32:13.
CRISPR gene drives allow scientists to change sequences of DNA and guarantee that the resulting edited genetic trait is inherited by future generations, opening up the possibility of altering entire species forever. More than anything, this technology has led to questions: How will this new power affect humanity? What are we going to use it to change? Are we gods now? Join journalist Jennifer Kahn as she ponders these questions and shares a potentially powerful application of gene drives: the development of disease-resistant mosquitoes that could knock out malaria and Zika.
Engineering the wild: Gene drives and intergenerational equity
6948J. Kuzma and L. Rawls, Jurimetrics, 56:279-296. 2016-03-01 16:08:02.
New genetic engineering methods are allowing scientists to insert genes into organisms that have the potential to spread themselves throughout natural populations upon the release of individuals carrying those genes. Gene drive technology is being researched and developed for purposes of reducing or eliminating human, ecological or agricultural pest populations, or immunizing other desirable or endangered species against pests and disease. The ability of humans to alter populations within ecosystems through genetic engineering raises issues associated with biodiversity and conservation that, in turn, may affect the abilities of current and future generations to use and enjoy the benefits of the natural world. Yet, children and future generations are not typically given voice in legal, policy, or ethical debates. This article examines several of the intergenerational equity issues posed by gene drive technologies. A typology of gene drive purposes and their potential ecological impacts is developed, followed by an examination of how they may intersect with concerns about intergenerational equity. To our knowledge, this analysis is the first to explore human intervention through genetically engineering populations in the wild and the impacts on future generations
Cheating evolution: engineering gene drives to manipulate the fate of wild populations
4083Champer, JB, A.; Akbari, O. S., Nature Reviews Genetics, 17:146-159. 2016-01-21 00:00:00.
Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne diseases such as malaria. Although several types of selfish genetic elements exist in nature, few have been successfully engineered in the laboratory thus far. With the discovery of RNA-guided CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) nucleases, which can be utilized to create, streamline and improve synthetic gene drives, this is rapidly changing. Here, we discuss the different types of engineered gene drives and their potential applications, as well as current policies regarding the safety and regulation of gene drives for the manipulation of wild populations.
Gene drive through a landscape: Reaction-diffusion models of population suppression and elimination by a sex ratio distorter
4081Beaghton, AB, P. J.; Burt, A., Theoretical Population Biology, 108:51-69. 2016-01-19 00:00:00.
Some genes or gene complexes are transmitted from parents to offsprihg at a greater-than-Mendelian rate, and can spread and persist in populations even if they cause some harm to the individuals carrying them. Such genes may be useful for controlling populations or species that are harmful. Driving-Y chromosomes may be particularly potent in this regard, as they produce a male-biased sex ratio that, if sufficiently extreme, can lead to population elimination. To better understand the potential of such genes to spread over a landscape, we have developed a series of reaction-diffusion models of a driving-Y chromosome in 1-D and radially-symmetric 2-D unbounded domains. The wild-type system at carrying capacity is found to be unstable to the introduction of driving-Y males for all models investigated. Numerical solutions exhibit travelling wave pulses and fronts, and analytical and semi-analytical solutions for the asymptotic wave speed under bounded initial conditions are derived. The driving-Y male invades the wild-type equilibrium state at the front of the wave and completely replaces the wild-type males, leaving behind, at the tail of the wave, a reduced- or zero-population state of females and driving-Y males only. In our simplest model of a population with one life stage and density-dependent mortality, wave speed depends on the strength of drive and the diffusion rate of Y-drive males, and is independent of the population dynamic consequences (suppression or elimination). Incorporating an immobile juvenile stage of fixed duration into the model reduces wave speed approximately in proportion to the relative time spent as a juvenile. If females mate just once in their life, storing sperm for subsequent reproduction, then wave speed depends on the movement of mated females as well as Y-drive males, and may be faster or slower than in the multiple-mating model, depending on the relative duration of juvenile and adult life stages. Numerical solutions are shown for parameter values that may in part be representative for Anopheles gambiae, the primary vector of malaria in sub-Saharan Africa. (C) 2015 The Authors. Published by Elsevier Inc.
Target Malaria has a killer in its sights: Eliminating the world’s deadliest disease has been a priority for decades, and, thanks to innovative gene-drive technology, Target Malaria is getting closer to achieving that goal
4080Banks, J, IEEE Pulse, 7:30-33. 2016-01-18 00:00:00.
The mosquito is the deadliest animal in the world (Figure 1). It is the main carrier of parasites that cause malaria, which is a bigger killer than any other disease in history; in fact, some blame malaria for the deaths of half the humans who have ever lived. Today, malaria continues to have a devastating effect on the health of millions of people.
Genetic engineering to eradicate invasive mice on islands: modeling the efficiency and ecological impacts
4079Backus, GAG, K., Ecosphere, 7:e01589. 2016-01-17 00:00:00.
Invasive rodents are usually eradicated from islands through the application of chemical toxicants that can harm surrounding ecosystems. A recently proposed alternative involves engineering a house mouse (Mus musculus) to carry a genetic construct that would cause a majority of its offspring to be male, many of which would be sterile. Releasing these genetically engineered mice to interbreed with an invasive population would reduce the number of fertile female mice until no more remain. We constructed a mathematical model to analyze the population dynamics of eradication with this genetically engineered mouse and determined its eradication efficiency through model analysis and simulations. Because genetically engineered mice would likely have a fitness disadvantage compared to wild mice, we found that they would need to be repeatedly released into the population to ensure complete eradication. However, if genetically engineered mice have a substantial survival advantage, we determined that the genetic construct could theoretically spread and eradicate a population after a single pulsed release onto the target island or after an engineered mouse escapes to a non-target location. Also, while the species specificity of genetic engineering avoids some of the non-target impacts of traditional eradication methods, ecological impacts could manifest indirectly. We compared several metrics to estimate potential transient impacts on the ecosystem and found that there is a trade-off between the speed of an eradication and the intensity of increased disruptive ecological interactions. Together, our results can inform safe and efficient ecological practices for eradication with developing genetic engineering technology.
Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies
4097Pugh, J, Journal of Medical Ethics, 42:578-581. 2016-01-15 00:00:00.
Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context.
Gene silencing and gene drive in dengue vector control
4095Paulraj, MGI, S.; Reegan, A. D., Indian Journal of Natural Products and Resources, 7:193-200. 2016-01-13 00:00:00.
Vector-borne diseases are the most feared diseases throughout the world. Mosquitoes are the prime human disease vectors as they are responsible for nearly one million human deaths every year. So they are declared as the most dangerous insects to mankind. Aedes aegypti and Ae. albopictus are the most significant mosquito species, because of their role in transmitting dengue virus. These blood feeding ectoparasites of man and other vertebrates have developed excellent adaptations to survive and multiply in and around human habitations. Chemical-based mosquito control method does not give good results due to rapid development of pesticide resistance in mosquitoes. The past four decades have witnessed the development of several alternate mosquito control methods. Genetic control technologies have been recently developed as efficient and ecofriendly methods. Inundate release of genetically modified mosquitoes with lethal or pathogen-resistant genes for population reduction is a recent technology in mosquito control programme. Recent developments in molecular and genome editing technologies have made it easy to produce thousands of transgenic mosquitoes for field release. The present review highlights various scientific reports and research findings on gene silencing and gene drive techniques in dengue mosquito control.
The Ecology and Evolutionary Dynamics of Meiotic Drive
4092Lindholm, AKD, K. A.; Firman, R. C.; Fishman, L.; Forstmeier, W.; Holman, L.; Johannesson, H.; Knief, U.; Kokko, H.; Larracuente, A. M.; Manser, A.; Montchamp-Moreau, C.; Petrosyan, V. G.; Pomiankowski, A.; Presgraves, D. C.; Safronova, L. D.; Sutter, A.; Unckless, R. L.; Verspoor, R. L.; Wedell, N.; Wilkinson, G. S.; Price, T. A. R., Trends in Ecology & Evolution, 31:315-326. 2016-01-10 00:00:00.
Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion.
Mechanisms of sex determination and transmission ratio distortion in Aedes aegypti
4089Hoang, KPT, T. M.; Ho, T. X.; Le, V. S., Parasites & Vectors, 9:49. 2016-01-07 00:00:00.
: More effective mosquito control strategies are urgently required due to the increasing prevalence of insecticide resistance. The sterile insect technique (SIT) and the release of insects carrying a dominant lethal allele (RIDL) are two proposed methods for environmentally-friendly, species-targeted population control. These methods may be more suitable for developing countries if producers reduce the cost of rearing insects. The cost of control programs could be reduced by producing all-male mosquito populations to circumvent the isolation of females before release without reducing male mating competitiveness caused by transgenes. Results: An RNAi construct targeting the RNA recognition motif of the Aedes aegypti transformer-2 (tra-2) gene does not trigger female-to-male sex conversion as commonly observed among dipterous insects. Instead, homozygous insects show greater mortality among m-chromosome-bearing sperm and mm zygotes, yielding up to 100 % males in the subsequent generations. The performance of transgenic males was not significantly different to wild-type males in narrow-cage competitive mating experiments. Conclusion: Our data provide preliminary evidence that the knockdown of Ae. aegypti tra-2 gene expression causes segregation distortion acting at the level of gametic function, which is reinforced by sex-specific zygotic lethality. This finding could promote the development of new synthetic sex distorter systems for the production of genetic sexing mosquito strains.
A CRISPR-Cas9 gene drive system-targeting female reproduction in the malaria mosquito vector Anopheles gambiae
4087Hammond, AG, R.; Kyrou, K.; Simoni, A.; Siniscalchi, C.; Katsanos, D.; Gribble, M.; Baker, D.; Marois, E.; Russell, S.; Burt, A.; Windbichler, N.; Crisanti, A.; Nolan, T., Nature Biotechnology, 34:78-83. 2016-01-05 00:00:00.
Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
Cas9-triggered chain ablation of cas9 as a gene drive brake
4106Wu, BL, L. Q.; Gao, X. J. J., Nature Biotechnology, 34:137-138. 2016-01-04 00:00:00.
We designed and synthesized a transgene system that we named Cas9-triggered chain ablation (CATCHA). The CATCHA transgene encodes a guide RNA (gRNA) that is expressed ubiquitously from a U6:2 promoter. The gRNA targets a site within the DNA sequence of cas9. The guide RNA is flanked by homology arms (of 1,042 bp and 1,003 bp) that match the cas9 sequences next to the gRNA-specified cleavage site (Fig. 1a). In the presence of both CATCHA and cas9, Cas9 proteins will be guided to cleave the cas9 genomic locus from which Cas9 proteins are expressed. Upon repair of the cleaved cas9 by homology-directed repair (HDR), the cas9 locus will be converted to CATCHA. Such conversion in heterozygous offspring favors amplification of CATCHA in the cas9- carrying population
Putting the brakes on CRISPR-Cas9 gene drive systems
4086Graham, DM, Lab Animal, 45:47-47. 2016-01-04 00:00:00.
The sudden emergence and worldwide adoption of CRISPR gene-editing technology confronts humanity with unprecedented opportunities and choices. CRISPR's transformative impact on our future understanding of biology, along with its potential to unleash control over the most fundamental of biological processes, is predictable by already achieved applications. Although its origin, composition, and function were revealed only recently, close to 3000 CRISPR-based publications have appeared including insightful and diversely focused reviews referenced here. Adding further to scientific and public awareness, a recent symposium addressed the ethical implications of interfacing CRISPR technology and human biology. However, the magnitude of CRISPR's rapidly emerging power mandates its broadest assessment. Only with the participation of a diverse and informed community can the most effective and humanity-positive CRISPR applications be defined. This brief review is aimed at those with little previous exposure to the CRISPR revolution. The molecules that constitute CRISPR's core components and their functional organization are described along with how the mechanism has been harnessed to edit genome structure and modulate gene function. Additionally, a glimpse into CRISPR's potential to unleash genetic changes with far-reaching consequences is presented.
The dawn of active genetics
4085Gantz, VMB, E., Bioessays, 38:50-63. 2016-01-03 00:00:00.
On December 18, 2014, a yellow female fly quietly emerged from her pupal case. What made her unique was that she had only one parent carrying a mutant allele of this classic recessive locus. Then, one generation later, after mating with a wild-type male, all her offspring displayed the same recessive yellow phenotype. Further analysis of other such yellow females revealed that the construct causing the mutation was converting the opposing chromosome with 95% efficiency. These simple results, seen also in mosquitoes and yeast, open the door to a new era of genetics wherein the laws of traditional Mendelian inheritance can be bypassed for a broad variety of purposes. Here, we consider the implications of this fundamentally new form of active genetics, its applications for gene drives, reversal and amplification strategies, its potential for contributing to cell and gene therapy strategies, and ethical/biosafety considerations associated with such active genetic elements.
What is a Gene Drive?
4715STAT, 2015-12-11 00:00:00.
This video produced by STAT, an e-news site focusing on health and medicine (https://www.statnews.com/). This video simply illustrates what geneticists mean by gene drive, and how homing-based gene drive work. (Note: it does not indicate that there are other mechanisms of gene drive.)
CRISPR-Cas9: Safeguarding Gene Drives
5501Harvard University, 2015-11-16 18:44:48.
In this animation, learn how effective safeguarding mechanisms developed at the Wyss Institute and Harvard Medical School can be applied to ensure gene drive research is done responsibly in the laboratory. These safeguards enable responsible scientific investigation into how gene drives could one day be leveraged for the greater good of human health, agriculture, and the environment.
Gene drive turns mosquitoes into malaria fighters
4123Pennisi, E, Science, 350:1014-1014. 2015-01-21 00:00:00.
The war against malaria has a new ally: a controversial technology for spreading genes throughout a population of animals. In the laboratory, researchers have harnessed a so-called gene drive to efficiently endow mosquitoes with genes that make them immune to the malaria parasite—and unable to spread it. On its own, gene drive won't get rid of malaria, but if successfully applied in the wild the method could help wipe out the disease, at least in some corners of the world. The approach “can bring us to zero [cases],” says Nora Besansky, a geneticist at the University of Notre Dame in South Bend, Indiana, who specializes in malaria-carrying mosquitoes
Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi
4115Gantz, VMJ, N.; Tatarenkova, O.; Fazekas, A.; Macias, V. M.; Bier, E.; James, A. A., Proceedings of the National Academy of Sciences of the United States of America, 112:e6736-e6743. 2015-01-13 00:00:00.
Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR). This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an similar to 17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into similar to 99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. In contrast to the efficient conversion in individuals expressing Cas9 only in the germ line, males and females derived from transgenic females, which are expected to have drive component molecules in the egg, produce progeny with a high frequency of mutations in the targeted genome sequence, resulting in near-Mendelian inheritance ratios of the transgene. Such mutant alleles result presumably from non-homologous end-joining (NHEJ) events before the segregation of somatic and germ-line lineages early in development. These data support the design of this system to be active strictly within the germ line. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.
The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations
4114V. M. Gantz and E. Bier, Science, 348:442. 2015-01-12 00:00:00.
Loss-of-function mutations may only produce a mutant phenotype when both copies of the gene are mutated. Gantz and Bier developed a method they call mutagenic chain reaction (MCR) that autocatalytically produces homozygous mutations. MCR uses the initial mutated allele to cause a mutation in the allele on the opposing chromosome and thus the homozygosity of the trait. MCR technology could have broad applications in diverse organisms.Science, this issue p. 442 An organism with a single recessive loss-of-function allele will typically have a wild-type phenotype, whereas individuals homozygous for two copies of the allele will display a mutant phenotype. We have developed a method called the mutagenic chain reaction (MCR), which is based on the CRISPR/Cas9 genome-editing system for generating autocatalytic mutations, to produce homozygous loss-of-function mutations. In Drosophila, we found that MCR mutations efficiently spread from their chromosome of origin to the homologous chromosome, thereby converting heterozygous mutations to homozygosity in the vast majority of somatic and germline cells. MCR technology should have broad applications in diverse organisms.
Opinion: Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat?
4131Webber, BLR, S.; Edwards, O. R., Proceedings of the National Academy of Sciences of the United States of America, 112:10565-10567. 2015-01-09 00:00:00.
Scientists have recognized the potential for applying gene drive technologies to the control of invasive species for several years, yet debate about the application of gene drive has been primarily restricted to mosquitoes. Recent developments in clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology have restarted discussions of using gene drive for invasive species control.
Safeguarding CRISPR-Cas9 gene drives in yeast
4111DiCarlo, JEC, A.; Dietz, S. L.; Esvelt, K. M.; Church, G. M., Nature Biotechnology, 33:1250-1255. 2015-01-09 00:00:00.
RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the prospect of unanticipated ecological change, demands caution. We report the efficacy of CRISPR-Cas9 gene drive systems in wild and laboratory strains of the yeast Saccharomyces cerevisiae. Furthermore, we address concerns surrounding accidental genome editing by developing and validating methods of molecular confinement that minimize the risk of unwanted genome editing. We also present a drive system capable of overwriting the changes introduced by an earlier gene drive. These molecular safeguards should enable the development of safe CRISPR gene drives for diverse organisms.
Gene drive overdrive
4110DeFrancesco, L, Nature Biotechnology, 33:1019-1021. 2015-01-08 00:00:00.
The recent publication of a simple procedure for creating a CRISPR-Cas9-mediated gene drive has some researchers sounding the alarm. What are the risks to populations in the wild and what precautions are necessary? Laura DeFrancesco investigates.
Modeling the manipulation of natural populations by the mutagenic chain reaction
4129Unckless, RLM, P. W.; Connallon, T.; Clark, A. G., Genetics, 201:425-431. 2015-01-07 00:00:00.
The use of recombinant genetic technologies for population manipulation has mostly remained an abstract idea due to the lack of a suitable means to drive novel gene constructs to high frequency in populations. Recently Gantz and Bier showed that the use of CRISPR/Cas9 technology could provide an artificial drive mechanism, the so-called mutagenic chain reaction (MCR), which could lead to rapid fixation of even a deleterious introduced allele. We establish the near equivalence of this system to other gene drive models and review the results of simple models showing that, when there is a fitness cost to the MCR allele, an internal equilibrium may exist that is usually unstable. In this case, introductions must be at a frequency above this critical point for the successful invasion of the MCR allele. We obtain estimates of fixation and invasion probabilities for the appropriate scenarios. Finally, we discuss how polymorphism in natural populations may introduce sources of natural resistance to MCR invasion. These modeling results have important implications for application of MCR in natural populations.
Safeguarding gene drive experiments in the laboratory
4107Akbari, OSB, H. J.; Bier, E.; Bullock, S. L.; Burt, A.; Church, G. M.; Cook, K. R.; Duchek, P.; Edwards, O. R.; Esvelt, K. M.; Gantz, V. M.; Golic, K. G.; Gratz, S. J.; Harrison, M. M.; Hayes, K. R.; James, A. A.; Kaufman, T. C.; Knoblich, J.; Malik, H. S.; Matthews, K. A.; O'Connor-Giles, K. M.; Parks, A. L.; Perrimon, N.; Port, F.; Russell, S.; Ueda, R.; Wildonger, J., Science, 349:927-929. 2015-01-05 00:00:00.
Gene drive systems promote the spread of genetic elements through populations by assuring they are inherited more often than Mendelian segregation would predict (see the figure). Natural examples of gene drive from Drosophila include sex-ratio meiotic drive, segregation distortion, and replicative transposition. Synthetic drive systems based on selective embryonic lethality or homing endonucleases have been described previously in Drosophila melanogaster (1–3), but they are difficult to build or are limited to transgenic populations. In contrast, RNAguided gene drives based on the CRISPR/Cas9 nuclease can, in principle, be constructed by any laboratory capable of making transgenic organisms (4). They have tremendous potential to address global problems in health, agriculture, and conservation, but their capacity to alter wild populations outside the laboratory demands caution (4–7). Just as researchers working with self-propagating pathogens must ensure that these agents do not escape to the outside world, scientists working in the laboratory with gene drive constructs are responsible for keeping them confined (4, 6, 7).
Systematic evaluation of Drosophila CRISPR tools reveals safe and robust alternatives to autonomous gene drives in basic research
4124Port, FM, N.; Bullock, S. L., G3-Genes Genomes Genetics, 5:1493-1502. 2015-01-02 00:00:00.
The Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR associated (CRISPR/Cas) technology allows rapid, site-specific genome modification in a wide variety of organisms. Proof-of-principle studies in Drosophila melanogaster have used various CRISPR/Cas tools and experimental designs, leading to significant uncertainty in the community about how to put this technology into practice. Moreover, it is unclear what proportion of genomic target sites can be modified with high efficiency. Here, we address these issues by systematically evaluating available CRISPR/Cas reagents and methods in Drosophila. Our findings allow evidence-based choices of Cas9 sources and strategies for generating knock-in alleles. We perform gene editing at a large number of target sites using a highly active Cas9 line and a collection of transgenic gRNA strains. The vast majority of target sites can be mutated with remarkable efficiency using these tools. We contrast our method to recently developed autonomous gene drive technology for somatic and germline genome engineering and conclude that optimized CRISPR with independent transgenes is as efficient, more versatile, and does not represent a biosafety risk.
Genetic Control of Mosquitoes.
5597Alphey, L., Annual Review of Entomology, 59:205-224. 2014-12-17 15:50:24.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
Genetic Engineering to the Rescue Against Invasive
11591K. Langin, National Geographic, 2014-07-18 15:37:46.
Genes for swatting tiger mosquitoes, defanging brown tree snakes, and deporting Asian carp, all nasty invasive species, sound like a swell idea. But the latest idea in eradication—genetic engineering—poses its own risks, warn biotechnology experts. Invasive species wreak havoc worldwide, disrupting native ecosystems and inflicting more than $120 billion in damages annually in the U.S. alone. Many economically—and environmentally—damaging species, such as those mosquitoes, snakes, and carp, defy removal with existing technology.
GM mosquitoes a ‘quantum leap’ towards tackling malaria
6940A. Vaughan, Guardian, 2014-06-10 15:54:00.
New technique injects mosquitoes with a gene that results in mostly male offspring, eventually leading to a population crash
Dynamics of a combined medea-underdominant population transformation system
4141Gokhale, CSR, R. G.; Reed, F. A., BMC Evolutionary Biology, 14:98. 2014-01-19 00:00:00.
: Transgenic constructs intended to be stably established at high frequencies in wild populations have been demonstrated to "drive" from low frequencies in experimental insect populations. Linking such population transformation constructs to genes which render them unable to transmit pathogens could eventually be used to stop the spread of vector-borne diseases like malaria and dengue. Results: Generally, population transformation constructs with only a single transgenic drive mechanism have been envisioned. Using a theoretical modelling approach we describe the predicted properties of a construct combining autosomal Medea and underdominant population transformation systems. We show that when combined they can exhibit synergistic properties which in broad circumstances surpass those of the single systems. Conclusion: With combined systems, intentional population transformation and its reversal can be achieved readily. Combined constructs also enhance the capacity to geographically restrict transgenic constructs to targeted populations. It is anticipated that these properties are likely to be of particular value in attracting regulatory approval and public acceptance of this novel technology.
A synthetic sex ratio distortion system for the control of the human malaria mosquito
4140Galizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A., Nature Communications, 5:3977. 2014-01-18 00:00:00.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito's X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies.
Genetic control of invasive fish: technological options and its role in integrated pest management
4158Thresher, REH, K.; Bax, N. J.; Teem, J.; Benfey, T. J.; Gould, F., Biological Invasions, 16:1201-1216. 2014-01-16 00:00:00.
Genetic options for the control of invasive fishes were recently reviewed and synthesized at a 2010 international symposium, held in Minneapolis/St. Paul, MN, USA. The only option currently available "off-the-shelf'' is triploidy, which can be used to produce sterile males for a release program analogous to those widely and successfully used for biological control of insect pests. However, the Trojan Y and several recombinant options that heritably distort pest population sex ratios are technologically feasible, are at or are close to proof-of-concept stage and are potentially much more effective than sterile male release programs. All genetic options at this stage require prolonged stocking programs to be effective, though gene drive systems are a potential for recombinant approaches. They are also likely to differ in their current degree of social acceptability, with chromosomal approaches (triploidy and Trojan Y) likely to be the most readily acceptable to the public and least likely to require changes in legislative or policy settings to be implemented. Modelling also suggests that the efficacy of any of these genetic techniques is enhanced by, and in turn non-additively enhance, conventional methods of pest fish control.
Heritable strategies for controlling insect vectors of disease
4136Burt, A, Philosophical Transactions of the Royal Society B-Biological Sciences, 369:20130432. 2014-01-14 00:00:00.
Mosquito-borne diseases are causing a substantial burden of mortality, morbidity and economic loss in many parts of the world, despite current control efforts, and new complementary approaches to controlling these diseases are needed. One promising class of new interventions under development involves the heritable modification of the mosquito by insertion of novel genes into the nucleus or of Wolbachia endosymbionts into the cytoplasm. Once released into a target population, these modifications can act to reduce one or more components of the mosquito population's vectorial capacity (e. g. the number of female mosquitoes, their longevity or their ability to support development and transmission of the pathogen). Some of the modifications under development are designed to be self-limiting, in that they will tend to disappear over time in the absence of recurrent releases (and hence are similar to the sterile insect technique, SIT), whereas other modifications are designed to be self-sustaining, spreading through populations even after releases stop (and hence are similar to traditional biological control). Several successful field trials have now been performed with Aedes mosquitoes, and such trials are helping to define the appropriate developmental pathway for this new class of intervention.
Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila: A theoretical exploration of Medea-dependent population suppression
4134Akbari, OSC, C. H.; Marshall, J. M.; Huang, H. X.; Antoshechkin, I.; Hay, B. A., ACS Synthetic Biology, 3:915-928. 2014-01-12 00:00:00.
Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.
Feasible introgression of an anti-pathogen transgene into an urban mosquito population without using gene-drive
4150Okamoto, KWR, M. A.; Gould, F.; Lloyd, A. L., PLOS Neglected Tropical Diseases, 8:e2827. 2014-01-08 00:00:00.
Introgressing anti-pathogen constructs into wild vector populations could reduce disease transmission. It is generally assumed that such introgression would require linking an anti-pathogen gene with a selfish genetic element or similar technologies. Yet none of the proposed transgenic anti-pathogen gene-drive mechanisms are likely to be implemented as public health measures in the near future. Thus, much attention now focuses instead on transgenic strategies aimed at mosquito population suppression, an approach generally perceived to be practical. By contrast, aiming to replace vector competent mosquito populations with vector incompetent populations by releasing mosquitoes carrying a single anti-pathogen gene without a gene-drive mechanism is widely considered impractical. Methodology/Principal FindingsHere we use Skeeter Buster, a previously published stochastic, spatially explicit model of Aedes aegypti to investigate whether a number of approaches for releasing mosquitoes with only an anti-pathogen construct would be efficient and effective in the tropical city of Iquitos, Peru. To assess the performance of such releases using realistic release numbers, we compare the transient and long-term effects of this strategy with two other genetic control strategies that have been developed in Ae. aegyptirelease of a strain with female-specific lethality, and a strain with both female-specific lethality and an anti-pathogen gene. We find that releasing mosquitoes carrying only an anti-pathogen construct can substantially decrease vector competence of a natural population, even at release ratios well below that required for the two currently feasible alternatives that rely on population reduction. Finally, although current genetic control strategies based on population reduction are compromised by immigration of wild-type mosquitoes, releasing mosquitoes carrying only an anti-pathogen gene is considerably more robust to such immigration. Conclusions/SignificanceContrary to the widely held view that transgenic control programs aimed at population replacement require linking an anti-pathogen gene to selfish genetic elements, we find releasing mosquitoes in numbers much smaller than those considered necessary for transgenic population reduction can result in comparatively rapid and robust population replacement. In light of this non-intuitive result, directing efforts to improve rearing capacity and logistical support for implementing releases, and reducing the fitness costs of existing recombinant technologies, may provide a viable, alternative route to introgressing anti-pathogen transgenes under field conditions.
The Trojan female technique: a novel, effective and humane approach for pest population control
13614N. J. Gemmell, A. Jalilzadeh, R. K. Didham, T. Soboleva and D. M. Tompkins, Proceedings of the Royal Society B: Biological Sciences, 280:20132549. 2013-12-22 13:07:01.
We use mathematical models to test a new twist on the SMT, using maternally inherited mitochondrial (mtDNA) mutations that affect male, but not female reproductive fitness. ‘Trojan females’ carrying suchmutations, and their female descendants, produce ‘sterile-male’-equivalents under natural conditions over multiple generations. We find that the Trojan female technique (TFT) has the potential to be a novel humane approach for pest control.
Engineering synthetic medea-based and threshold- dependent underdominance-based gene drive systems in mosquitoes
4163Akbari, OM, J.; Antoshechkin, I.; Matzen, K.; Papathanos, P.; Kennedy, K.; Ward, C.; Chen, C. H.; Guo, M.; Hay, B., Pathogens and Global Health, 107:442-442. 2013-01-21 00:00:00.
Mosquito population replacement requires gene drive mechanisms in order to spread linked genes, mediating disease refractoriness, through wild populations. Medea is predicted to be a low threshold gene drive mechanism, able to spread from low initial frequency. Such a system is ideal when the goal is area-wide population replacement. However, once released, it is difficult to restore the pre-transgenic state, if desired. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread provide an attractive alternative because they bring about local, but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal- effect lethal underdominance (UDMEL). We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. We will describe the dynamics of the UDMEL system, and our progress in transferring Medea and UDMEL into Aedes aegypti.
Modelling the spatial spread of a homing endonuclease gene in a mosquito population
4177North, AB, A.; Godfray, H. C. J., Journal of Applied Ecology, 50:1216-1225. 2013-01-15 00:00:00.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean-field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail.Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.
Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populations
4175Legros, MX, C. G.; Morrison, A.; Scott, T. W.; Lloyd, A. L.; Gould, F., PLOS One, 8:e83354. 2013-01-13 00:00:00.
Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.
The design and in vivo evaluation of engineered I-OnuI-based enzymes for HEG gene drive
4169Chan, YST, R.; Jarjour, J.; Huen, D. S.; Stoddard, B. L.; Russell, S., PLOS One, 8:e74254. 2013-01-07 00:00:00.
The homing endonuclease gene (HEG) drive system, a promising genetic approach for controlling arthropod populations, utilises engineered nucleases to spread deleterious mutations that inactivate individual genes throughout a target population. Previous work with a naturally occurring LAGLIDADG homing endonuclease (I-SceI) demonstrated its feasibility in both Drosophila and Anopheles. Here we report on the next stage of this strategy: the redesign of HEGs with customized specificity in order to drive HEG-induced 'homing' in vivo via break-induced homologous recombination. Variants targeting a sequence within the Anopheles AGAP004734 gene were created from the recently characterized I-OnuI endonuclease, and tested for cleavage activity and frequency of homing using a model Drosophila HEG drive system. We observed cleavage and homing at an integrated reporter for all endonuclease variants tested, demonstrating for the first time that engineered HEGs can cleave their target site in insect germline cells, promoting targeted mutagenesis and homing. However, in comparison to our previously reported work with I-SceI, the engineered I-OnuI variants mediated homing with a reduced frequency, suggesting that site-specific cleavage activity is insufficient by itself to ensure efficient homing. Taken together, our experiments take a further step towards the development of a viable HEG-based population control strategy for insects.
Optimising homing endonuclease gene drive performance in a semi-refractory species: The Drosophila melanogaster experience
4168Chan, YSH, D. S.; Glauert, R.; Whiteway, E.; Russell, S., PLOS One, 8:e54130. 2013-01-06 00:00:00.
Homing endonuclease gene (HEG) drive is a promising insect population control technique that employs meganucleases to impair the fitness of pest populations. Our previous studies showed that HEG drive was more difficult to achieve in Drosophila melanogaster than Anopheles gambiae and we therefore investigated ways of improving homing performance in Drosophila. We show that homing in Drosophila responds to increased expression of HEGs specifically during the spermatogonia stage and this could be achieved through improved construct design. We found that 39-UTR choice was important to maximise expression levels, with HEG activity increasing as we employed Hsp70, SV40, vasa and beta Tub56D derived UTRs. We also searched for spermatogonium-specific promoters and found that the Rcd-1r promoter was able to drive specific expression at this stage. Since Rcd-1 is a regulator of differentiation in other species, it suggests that Rcd-1r may serve a similar role during spermatogonial differentiation in Drosophila. Contrary to expectations, a fragment containing the entire region between the TBPH gene and the bgcn translational start drove strong HEG expression only during late spermatogenesis rather than in the germline stem cells and spermatogonia as expected. We also observed that the fraction of targets undergoing homing was temperature-sensitive, falling nearly four-fold when the temperature was lowered to 18 degrees C. Taken together, this study demonstrates how a few simple measures can lead to substantial improvements in the HEG-based gene drive strategy and reinforce the idea that the HEG approach may be widely applicable to a variety of insect control programs.
Germline excision of transgenes in Aedes aegypti by homing endonucleases
4165Aryan, AA, M. A. E.; Myles, K. M.; Adelman, Z. N., Scientific Reports, 3:1603. 2013-01-03 00:00:00.
Aedes (Ae.) aegypti is the primary vector for dengue viruses (serotypes1-4) and chikungunya virus. Homing endonucleases (HEs) are ancient selfish elements that catalyze double-stranded DNA breaks (DSB) in a highly specific manner. In this report, we show that the HEs Y2-I-AniI, I-CreI and I-SceI are all capable of catalyzing the excision of genomic segments from the Ae. aegypti genome in a heritable manner. Y2-I-AniI demonstrated the highest efficiency at two independent genomic targets, with 20-40% of Y2-I-AniI-treated individuals producing offspring that had lost the target transgene. HE-induced DSBs were found to be repaired via the single-strand annealing (SSA) and non-homologous end-joining (NHEJ) pathways in a manner dependent on the availability of direct repeat sequences in the transgene. These results support the development of HE-based gene editing and gene drive strategies in Ae. aegypti, and confirm the utility of HEs in the manipulation and modification of transgenes in this important vector.
A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations
4164Akbari, OSM, K. D.; Marshall, J. M.; Huang, H. X.; Ward, C. M.; Hay, B. A., Current Biology, 23:671-677. 2013-01-02 00:00:00.
Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency [1-3]. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals [4-6]. These features are likely to be important in many social and regulatory contexts [7-10]. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UDMEL), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UDMEL has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation.
Ethical issues in field trials of genetically modified disease-resistant mosquitoes
13538D. B. Resnik, Developing World Bioethics, 14:37-46. 2012-07-29 19:12:07.
Mosquito-borne diseases take a tremendous toll on human populations, especially in developing nations. In the last decade, scientists have developed mosquitoes that have been genetically modified to prevent transmission of mosquito-borne diseases, and field trials have been conducted. Some mosquitoes have been rendered infertile, some have been equipped with a vaccine they transmit to humans, and some have been designed to resist diseases.
The Nagoya – Kuala Lumpur Supplementary Protocol on Liability and Redress to the Cartagena Protocol on Biosafety
5660Secretariat of the Convention on Biological Diversity, Convention on Biodiversity, 2011:1-16. 2011-12-17 18:41:08.
Adopted as a supplementary agreement to the Cartagena Protocol on Biosafety, the Supplementary Protocol aims to contribute to the conservation and sustainable use of biodiversity by providing international rules and procedures in the field of liability and redress relating to living modified organisms, as stated in its Article 1. The Protocol applies to damage resulting from living modified organism which find their origin in a transboundary movement (Article 3). The Supplementary Protocol provides a definition of ‘damage’, referring to an adverse effect on the conservation and sustainable use of biological diversity that is measurable or otherwise observable and significant, taking also into account risks to human health. It provides for an indicative list of factors that should be used to determine the significance of an adverse effect. The Supplementary Protocol requires in Article 4 that a causal link between the damage and the living modified organism be established. States must require the appropriate operator or operators to take response measures in the event of damage resulting from living modified organisms which find their origin in a transboundary movement, as set out in Article 5. The ‘operator’ is defined as any person in direct or indirect control of the living modified organism. The operator must also take response measures where there is a sufficient likelihood that damage will result if timely response measures are not taken. Response measures may also be taken by the competent authority, for example when the operator has failed to do so. In such cases, the competent authority may recover the expenses and costs of such measures from the operator. In addition to the obligation to provide for response measures, Parties may develop civil liability rules and procedures to address damage. The Supplementary Protocol defines ‘response measures’ as reasonable actions to prevent, minimize, contain, mitigate or otherwise avoid damage, as appropriate, or reasonable actions to restore biological diversity. In addition to imposing a requirement for response measures, the Supplementary Protocol obliges Parties to continue to apply existing legislation on civil liability or to develop specific legislation concerning liability and redress for material or personal damage associated with damage to the conservation and sustainable use of biological diversity, as defined in the Supplementary Protocol. As response measures can be imposed by the competent administrative authority, rather than by a judicial body, the Supplementary Protocol is known as having introduced an ‘administrative approach’ to liability and redress.
Field performance of engineered male mosquitoes
6401A. F. Harris, D. Nimmo, A. R. McKemey, N. Kelly, S. Scaife, C. A. Donnelly, C. Beech, W. D. Petrie and L. Alphey, Nature Biotechnology, 29:1034-1037. 2011-10-30 16:54:55.
Mass-release of sterile male mosquitoes is a promising option for controlling dengue and malaria, but it has never been shown that lab-raised transgenic males can compete effectively with their wild counterparts outside laboratory conditions. Promising results from a restricted field trail now suggest the feasibility of extending the approach for large-scale mosquito-control programs.
Insect population control by homing endonuclease-based gene drive: An evaluation in Drosophila melanogaster
4201Chan, YSN, D. A.; Huen, D. S.; Russell, S., Genetics, 188:33-44. 2011-01-19 00:00:00.
Insects play a major role as vectors of human disease as well as causing significant agricultural losses. Harnessing the activity of customized homing endonuclease genes (HEGs) has been proposed as a method for spreading deleterious mutations through populations with a view to controlling disease vectors. Here, we demonstrate the feasibility of this method in Drosophila melanogaster, utilizing the well-characterized HEG, I-SceI. In particular, we show that high rates of homing can be achieved within spermatogonia and in the female germline. We show that homed constructs continue to exhibit HEG activity in the subsequent generation and that the ectopic homing events required for initiating the strategy occur at an acceptable rate. We conclude that the requirements for successful deployment of a HEG-based gene drive strategy can be satisfied in a model dipteran and that there is a reasonable prospect of the method working in other dipterans. In characterizing the system we measured repair outcomes at the spermatogonial, spermatocyte, and spermatid stages of spermatogenesis. We show that homologous recombination is restricted to spermatogonia and that it immediately ceases when they become primary spermatocytes, indicating that the choice of DNA repair pathway in the Drosophila testis can switch abruptly during differentiation.
A synthetic homing endonuclease-based gene drive system in the human malaria mosquito
4211Windbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A., Nature, 473:212-215. 2011-01-09 00:00:00.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito's ability to serve as a disease vector(4-7). The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations(8). We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose(9). Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions(10) and the homing endonuclease gene I-SceI(11-13), can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.
Multi-Locus Assortment (MLA) for transgene dispersal and elimination in mosquito populations
4230Rasgon, JL, PLOS One, 4:e5833. 2009-01-08 00:00:00.
: Replacement of wild-type mosquito populations with genetically modified versions is being explored as a potential strategy to control vector-borne diseases. Due to lower expected relative fitness of transgenic individuals, transgenes must be driven into populations for these scenarios to be successful. Several gene drive mechanisms exist in a theoretical sense but none are currently workable in mosquitoes. Even if strategies were workable, it would be very difficult to recall released transgenes in the event of unforeseen consequences. What is needed is a way to test transgenes in the field for feasibility, efficacy and safety prior to releasing an active drive mechanism. Methodology/Principal Findings: We outline a method, termed Multi-locus assortment (MLA), to spread transgenes into vector populations by the release of genetically-modified mosquitoes carrying multiple stable transgene inserts. Simulations indicate that [1] insects do not have to carry transgenes at more than 4 loci, [2] transgenes can be maintained at high levels by sequential small releases, the frequency of which depends on the construct fitness cost, and [3] in the case of unforeseen negative non-target effects, transgenes can be eliminated from the population by halting transgenic releases and/or mass releases of wild-type insects. We also discuss potential methods to create MLA mosquito strains in the laboratory. Conclusions/Significance: While not as efficient as active drive mechanisms, MLA has other advantages: [1] MLA strains can be constructed for some mosquito species with currently-available technology, [2] MLA will allow the ecological components of transgenic mosquito releases to be tested before actual gene drive mechanisms are ready to be deployed, [3] since MLA is not self-propagating, the risk of an accidental premature release into nature is minimized, and [4] in the case that active gene drive mechanisms prove impossible to develop, the MLA approach can be used as a back-up transgene dispersal mechanism for disease control efforts in some systems.
Researchers eliminate mosquito population through CRISPR gene editing technology
4566Goss, L, Pharmafile, 2008-09-27 00:00:00.
Researchers at Imperial College London have been able to wipe out a population of mosquitoes through ‘gene drive’ technology. The study, published in the journal Nature Biotechnology saw a CRISPR edited gene being used to prevent female mosquitos from being born.; ; As such after eight generations, an entirely male population had been born, which was then unable to breed. The technology may now be used to block the reproductive capabilities of mosquitoes in the real world, in order to prevent the transmission of malaria.
The Impact of Dissociation on Transposon-Mediated Disease Control Strategies
23831J. M. Marshall, Genetics, 178:1673-1682. 2008-03-01 23:54:22.
Vector-borne diseases such as malaria and dengue fever continue to be a major health concern through much of the world. The emergence of chloroquine-resistant strains of malaria and insecticide-resistant mosquitoes emphasize the need for novel methods of disease control. Recently, there has been much interest in the use of transposable elements to drive resistance genes into vector populations as a means of disease control. One concern that must be addressed before a release is performed is the potential loss of linkage between a transposable element and a resistance gene. Transposable elements such as P and hobo have been shown to produce internal deletion derivatives at a significant rate, and there is concern that a similar process could lead to loss of the resistance gene from the drive system following a transgenic release. Additionally, transposable elements such as Himar1 have been shown to transpose significantly more frequently when free of exogenous DNA. Here, we show that any transposon-mediated gene drive strategy must have an exceptionally low rate of dissociation if it is to be effective. Additionally, the resistance gene must confer a large selective advantage to the vector to surmount the effects of a moderate dissociation rate and transpositional handicap.
A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
4238Gould, FH, Yunxin; Legros, Mathieu; Lloyd, Alun L., Proceedings of the Royal Society B: Biological Sciences, 275:2823-2829. 2008-01-16 00:00:00.
A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2?:?1 release (engineered?:?wild) or after four 1?:?2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.
Broadening the application of evolutionarily based genetic pest management
4237Gould, F, Evolution, 62:500-510. 2008-01-15 00:00:00.
Insect- and tick-vectored diseases such as malaria, dengue fever, and Lyme disease cause human suffering, and current approaches for prevention are not adequate. Invasive plants and animals such as Scotch broom, zebra mussels, and gypsy moths continue to cause environmental damage and economic losses in agriculture and forestry Rodents transmit diseases and cause major pre- and postharvest losses, especially in less affluent countries. Each of these problems might benefit from the developing field of Genetic Pest Management that is conceptually based on principles of evolutionary biology This article briefly describes the history of this field, new molecular tools in this field, and potential applications of those tools. There will be a need for evolutionary biologists to interact with researchers and practitioners in a variety of other fields to determine the most appropriate targets for genetic pest management, the most appropriate methods for specific targets, and the potential of natural selection to diminish the effectiveness of genetic pest management. In addition to producing environmentally sustainable pest management solutions, research efforts in this area could lead to new insights about the evolution of selfish genetic elements in natural systems and will provide students with the opportunity to develop a more sophisticated understanding of the role of evolutionary biology in solving societal problems.
The population genetics of using homing endonuclease genes in vector and pest management
4234Deredec, AB, A.; Godfray, H. C. J., Genetics, 179:2013-2026. 2008-01-12 00:00:00.
Homing endonuclease genes (HEGs) encode proteins that in the heterozygous state cause double- strand breaks in the homologous chromosome at the precise position opposite the HFG. If the double-strand break is repaired using the homologous chromosome, the HEG becomes homozygous, and this represents it Powerful genetic drive mechanism that might he used as it tool managing vector or pest populations. HEGs may be used to decrease population fitness to drive down population densities (possibly causing local extinction) or, in disease vectors, to knock out a gene required for pathogen transmission. The relative advantages of HEGs thia target viability or fecundity, that are active in one sex or both, and whose target. is expressed before or after homing are explored. The conditions under which escape mutants arise are also analyzed. A different strategy is to place HEGs on the Y chromosome that cause one, or more breaks on the X chromosome and so disrupt. sex ratio. This strategy can cause severe sex-ratio biases with efficiencies that depend on the details of sperm Competition and zygote mortality. This strategy is probably less susceptible to escape mutants, especially when multiple X shredders are used.
Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: Recommendations of a scientific working group
4232Benedict, MDA, P.; Dobson, S.; Gottlieb, M.; Harrington, L.; Higgs, S.; James, A.; James, S.; Knols, B.; Lavery, J.; O'Neill, S.; Scott, T.; Takken, W.; Toure, Y.; Core Working Grp Guidance, Containe, Vector-Borne and Zoonotic Diseases, 8:127-166. 2008-01-10 00:00:00.
The following recommendations represent the response of a group of involved scientists to the need for guidance to aid researchers, government authorities, and community leaders as they consider the design and implementation of field trials to assess the safety and efficacy of genetic strategies for reducing the transmission of diseases by mosquito vectors. Guidance is provided for contained (caged) field trials of genetically-engineered (GE) vector mosquitoes that are fertile and contain novel genetic constructs designed to spread through natural mosquito populations (“gene drive systems”). An effort is made to raise the practical issues that must be considered in advance of such testing, provide generalized recommendations based on currently available information, and identify “points to consider” regarding additional information that may be required in order to make informed decisions on a case-by-case basis. This guidance is intended to clarify the pathway for further assessment of the potential utility of such GE mosquitoes as a tool for the improvement of public health in disease-endemic regions.
Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae
4247Windbichler, NP, P. A.; Crisanti, A., PLOS Genetics, 4:1-9. 2008-01-05 00:00:00.
We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases.
Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos
4259Windbichler, NP, P. A.; Catteruccia, F.; Ranson, H.; Burt, A.; Crisanti, A., Nucleic Acids Research, 35:5922-5933. 2007-01-17 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of these properties, HEGs are regarded as promising candidates to transfer genetic modifications from engineered laboratory mosquitoes to wild-type populations including Anopheles gambiae the vector of human malaria. Here we show that I-SceI and I-PpoI homing endonucleases cleave their recognition sites with high efficiency inA. gambiae cells and embryos and we demonstrate HEG-induced homologous and non-homologous repair events in a variety of functional assays. We also propose a gene drive system for mosquitoes that is based on our finding that I-PpoI cuts genomic rDNA located on the X chromosome in A. gambiae, which could be used to selectively incapacitate X-carrying spermatozoa thereby imposing a severe male-biased sex ratio.
Genetic strategies for controlling mosquito-borne diseases
6191F. Gould, K. Magori and Y. Huang, American Scientist, 94:238. 2006-05-03 19:19:14.
Malaria kills more than a million people each year, primarily children under the age of six. Dengue fever is less deadly, but an outbreak can debilitate millions of people and easily overwhelm doctors and hospitals in tropical cities
Gene drive systems for insect disease vectors
4269Sinkins, SPG, F., Nature Reviews Genetics, 7:427-435. 2006-01-07 00:00:00.
The elegant mechanisms by which naturally occurring selfish genetic elements, such as transposable elements, meiotic drive genes, homing endonuclease genes and Wolbachia, spread at the expense of their hosts provide some of the most fascinating and remarkable subjects in evolutionary genetics. These elements also have enormous untapped potential to be used in the control of some of the world's most devastating diseases. Effective gene drive systems for spreading genes that can block the transmission of insect-borne pathogens are much needed. Here we explore the potential of natural gene drive systems and discuss the artificial constructs that could be envisaged for this purpose.
History of the Sterile Insect Technique
6360Klassen, W. and C. F. Curtis, Sterile Insect Technique: Principles and Practice in Area-Wide Integrated Pest Managemen, 2005:3-36.. 2005-03-09 20:56:59.
During the 1930s and 1940s the idea of releasing insects of pest species to introduce sterility (sterile insect technique or SIT) into wild populations, and thus control them, was independently conceived in three extremely diverse intellectual environments. The key researchers were A. S. Serebrovskii at Moscow State University, F. L. Vanderplank at a tsetse field research station in rural Tanganyika (now Tanzania), and E. F. Knipling of the United States Department of Agriculture. Serebrovskii’s work on chromosomal translocations for pest population suppression could not succeed in the catastrophic conditions in the USSR during World War II, after which he died. Vanderplank used hybrid sterility to suppress a tsetse population in a large field experiment, but lacked the resources to develop this method further. Knipling and his team exploited H. J. Muller’s discovery that ionizing radiation can induce dominant lethal mutations, and after World War II this approach was applied on an area-wide basis to eradicate the New World screwworm Cochliomyia hominivorax (Coquerel) in the USA, Mexico, and Central America. Since then very effective programmes integrating the SIT have been mounted against tropical fruit flies, some species of tsetse flies Glossina spp., the pink bollworm Pectinophora gossypiella (Saunders), and the codling moth Cydia pomonella (L.). In non-isolated onion fields in the Netherlands, the onion maggot Delia antiqua (Meigen) has since 1981 been suppressed by the SIT. In the 1970s there was much research conducted on mosquito SIT, which then went into “eclipse”, but now appears to be reviving. Development of the SIT for use against the boll weevil Anthonomus grandis grandis Boheman and the gypsy moth Lymantria dispar (L.) has ended, but it is in progress for two sweetpotato weevil species, Cylas formicarius (F.) and Euscepes postfasciatus (Fairmaire), the false codling moth Cryptophlebia leucotreta (Meyrick), the carob moth Ectomyelois ceratoniae (Zeller), the cactus moth Cactoblastis cactorum (Berg), the Old World screwworm Chrysomya bezziana (Villeneuve), additional Glossina spp., other Anastrepha spp. and Bactrocera spp. fruit flies, and other pest insects.
Population dynamics of transposable elements: Copy number regulation and species invasion requirements
4282Struchiner, CJK, M. G.; Ribeiro, J. M. C., Journal of Biological Systems, 13:455-475. 2005-01-20 00:00:00.
A deterministic population dynamics model of the spread of transposable elements (TE) in sexually reproducing populations is presented. The population is modeled by a three-parameter equation describing host reproductive capacity, population size and the strength of the density dependence, while TE dynamics were modeled based also on three parameters, the maximum ability of the element to copy itself in the absence of regulation (T(0)), the regulatory effect of copy number decreasing transposition (C(0.5)), and the deleterious effect of each new transposition on host fitness (d). The mechanism of transposition control is therefore a function of the number of new TE copies. Our results indicate that non-regulated elements cannot fix in host populations, and that prediction of stable copy number following successful invasion is mainly a function of the combination of T(0) and C(0.5) values. Fitness reduction does not affect the final copy number after successful invasion of the element. Fitness reduction, however, will affect the surface of the {T(0) x C(0.5)} parameter space leading to successful invasion of the TE. Invasion of host populations by eight or more individuals containing elements with appropriate parameters will lead to successful element fixation at any size of the host population. Host population extinction due to the invasion of TE's is observed in a small area of the {T(0) x C(0.5)} parameter space. These results are qualitatively preserved under alternative choices for the shape of the functions defining regulation of transposition and distinct sets of parameters determining host population dynamics.
Transposable element insertion location bias and the dynamics of gene drive in mosquito populations
4280Rasgon, JLG, F., Insect Molecular Biology, 14:493-500. 2005-01-18 00:00:00.
Some vector-borne disease control strategies using transgenic mosquitoes require transgene spread to high frequency in populations. Transposable elements (TEs) are DNA sequences that replicate and transpose within the genomes of other organisms and may therefore be represented in the next generation in higher frequencies than predicted by Mendelian segregation. This over-representation has allowed some TEs to spread through natural populations. Transgenes incorporated within a TE sequence are expected to be driven into populations as long as there is a positive balance between fitness costs and over-representation. Models have been used to examine parameters that affect this balance but did not take into account biased insertion of TEs to linked sites in the genome. A simulation model was created to examine the impact of insertion bias on TE spread in mosquito populations. TEs that induce no fitness costs are predicted to increase in frequency over a wide range of parameter values but spread is slower for lower levels of transposition and non-local movement. If TEs are costly, high proportions of local movement can slow or halt spread. To function as a robust transgene drive mechanism a TE should replicate and transpose > 10%/insert/generation, induce < 1% fitness cost/insert, and move preferentially to unlinked sites in the genome.
Gene drive systems in mosquitoes: rules of the road
4275James, AA, Trends in Parasitology, 21:64-67. 2005-01-13 00:00:00.
Population replacement strategies for controlling transmission of mosquito-borne diseases call for the introgression of antipathogen effector genes into vector populations. It is anticipated that these genes, if present at high enough frequencies, will impede transmission of the target pathogens and result in reduced human morbidity and mortality. Recent laboratory successes in the development of virus- and protozoan-resistant mosquito strains make urgent research of gene drive systems capable of moving effector genes into wild populations. A systematic approach to developing safe and effective gene drive systems that includes defining the requirements of the system, identifying naturally occurring or synthetic genetic mechanisms for gene spread upon which drive systems can be based and the successful adaptation of a mechanism to a drive system, should mitigate concerns about using genetically engineered mosquitoes for disease control.
Reinvestigation of an endogenous meiotic drive system in the mosquito, Aedes aegypti (Diptera : Culicidae)
4295Mori, AC, D. D.; Graham, D. H.; Severson, D. W., Journal of Medical Entomology, 41:1027-1033. 2004-01-13 00:00:00.
We have initiated efforts to determine the molecular basis for the M-D meiotic drive system in the mosquito, Aedes aegypti. The effect of the M-D gene is a highly male-biased sex ratio, but varies depending on the frequency and sensitivity of a susceptible responder m(s) allele. The M-D system has potential as a mechanism for driving trangenes for pathogen resistance into natural Ae. aegypti populations. Because all previously existing laboratory strains carrying the M-D gene have been lost, we have selected for a new strain, T37, that carries a strong driver. Matings between T37 males and drive-susceptible in m(s) females result in progeny with highly biased sex ratios, wherein only approximate to14.7% females are produced. We discuss the potential for identifying M-D candidate genes based on comparisons with the well-described Drosophila melanogaster segregation distorter (SD) meiotic drive system and considerations for release of transgenic Ae. aegypti into natural populations where M-D and insensitive m(i) alleles are likely segregating.
Site-specific selfish genes as tools for the control and genetic engineering of natural populations
4306Burt, A, Proceedings of the Royal Society B-Biological Sciences, 270:921-928. 2003-01-04 00:00:00.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.
Malaria Control with Genetically Manipulated Insect Vectors
16035L. Alphey, C. B. Beard, P. Billingsley, M. Coetzee, A. Crisanti, C. Curtis, P. Eggleston, C. Godfray, J. Hemingway, M. Jacobs-Lorena, A. A. James, F. C. Kafatos, L. G. Mukwaya, M. Paton, J. R. Powell, W. Schneider, T. W. Scott, B. Sina, R. Sinden, S. Sink, Science, 298:119. 2002-10-04 19:49:32.
At a recent workshop, experts discussed the benefits, risks, and research priorities associated with using genetically manipulated insects in the control of vector-borne diseases.
Cartagena Protocol on Biosafety to the Convention on Biological Diversity
5665Secretariat of the Convention on Biological Diversity, Convention on Biodiversity, 2000:1-19. 2000-12-17 18:48:56.
The Cartagena Protocol on Biosafety to the Convention on Biological Diversity is an international agreement which aims to ensure the safe handling, transport and use of living modified organisms (LMOs) resulting from modern biotechnology that may have adverse effects on biological diversity, taking also into account risks to human health. It was adopted on 29 January 2000 and entered into force on 11 September 2003.
Malaria: existing methods of vector control and molecular entomology
4369Curtis, CFT, H., British Medical Bulletin, 54:311-325. 1998-01-07 00:00:00.
In general, the most effective means of malaria vector control is the killing of adult mosquitoes with a residual insecticide applied to bednets or sprayed on house walls and ceilings. Major reductions in all-cause child mortality have been achieved in Africa by these means. In some circumstances, personal protection and larval control may also make a contribution. We discuss the prospects of genetic control by release of sterile male mosquitoes or driving genes for refractoriness to malaria into wild populations. Many major malaria vectors belong to complexes of sibling species which differ in vectorial and biological characteristics. Distinguishing the species by cytogenetic or molecular methods is important for epidemiological studies and could improve the targeting of control.
Gene transfer into the Medfly, Ceratitis capitata, using a Drosophila hydei transposable element.
6269T. G. Loukeris, I. Livadaras, B. Arca, S. Zabalou and C. Savakis, Science, 270:2002-2005. 1995-12-22 16:35:47.
Exogenous functional DNA was introduced into the germline chromosomes of the Mediterranean fruit fly (medfly) Ceratitis capitata with a germline transformation system based on the transposable element Minos from Drosophila hydei. Transformants were identified as phenotypic revertants of a white-eyed mutation carried by the recipient strain. Clusters of transformants were detected among the progeny of 390 individuals screened for germline transformation. Five independent and phenotypically active integration events were identified, in each of which a single copy of the transposon was inserted into a different site of the medfly genome. Molecular analysis indicates that they represent transposase-mediated insertions of the transposon into medfly chromosomes.
Selfish DNA as method of pest control
4414Hastings, IM, Philosophical Transactions of the Royal Society B-Biological Sciences, 344:313-324. 1994-01-12 00:00:00.
The inheritance of most genes is tightly controlled, governed by the rules of mendelian inheritance if nuclear or uniparental inheritance if cytoplasmic. A few notable genes and cytoplasmic genomes have escaped this regulation. Such genes may spread by increasing their own rate of transmission despite reducing host fitness and may be regarded as 'selfish'. Their population genetics are described and it appears they may impose a significant genetic load on the host population. Modern molecular techniques may enable similar loads to be imposed on pest species either by transferring selfish genes between species, or by linking deleterious genes to a selfish locus. Alternatively, 'modifier' genes that eliminate the virulent, or disease vectorial capacity, of the pest population may be introduced by linkage to a selfish locus. Selfish elements present in multiple copies may be preferable to single-copy elements as the former are capable of a larger reduction in host fitness. The practical application of these agents depends on five factors: (i) the rate of 'reversion' to a non-selfish form; (ii) the evolution of host repressor systems; (iii) their effect on host fitness, which determines their rate of invasion; (iv) the mechanism regulating host population size in the field; and (v) their ease of manipulation in the laboratory. The first two factors are the most uncertain in most systems, but should be amenable to experimental analysis. It is proposed that the development of such techniques may result in powerful new methods of population control which may be applied to both agricultural pests and disease vectors.
Can transposable elements be used to drive disease refractoriness genes into vector populations?
6271M. G. Kidwell and J. M. C. Ribeiro, Parasitology Today, 8:325-329. 1992-01-08 16:40:55.
A number of biological procedures are currently being considered as alternatives to insecticide-based methods for the control of insect vectors of disease. Among these are the adaptation of various genetic mechanisms to drive genes of interest, such as refractoriness to malaria in mosquitoes, into natural populations, for vector control purposes. Here, Margaret Kidwell and Jose Ribeiro develop a rationale for the possible use of transposable genetic elements, one of these potential drive mechanisms, and some of the problems being faced in seeking to determine the feasibility of such a strategy are described.
Genetics-driving genes and chromosomes
4463Charlesworth, B, Nature, 332:394-395. 1988-01-21 00:00:00.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew attention to the fact that it operates as an evolutionary force which can cause an increase in the population frequency of the allele or chromosome which is favoured in transmission, even if it confers a disadvantage on its carriers in terms of fitness at the level of the individual
Methods for replacement of malaria vector populations
4464Curtis, CFG, P. M., American Journal of Tropical Medicine and Hygiene, 91:43-48. 1988-01-02 00:00:00.
The prospects are reviewed of replacement of malaria vector populations by harmless mosquito populations by means of: (i) ecologically competitive non-vector species; (ii) natural selection due to the harmfulness of being infected; (iii) selection for insecticide resistance genes; (iv) meiotic drive; (v) negative heterosis; and (vi) hybrid dysgenesis. Serious difficulties exist with all of these approaches. At present 'dilution', i.e. release of insects carrying the desired genes without any system for forcing population replacement is the only available method. It avoids the disadvantage that, in constructing elaborate genetic 'packages', factors for low fitness may be irreversibly incorporated into them. It is debatable whether release of males only or both sexes should be attempted.
A cage replacement experiment involving introduction of genes for refractoriness to Plasmodium-yoelii-nigeriensis into a population of Anopheles gambiae (Diptera, Culicidae)
6230P. M. Graves and C. F. Curtis, Journal of Medical Entomology, 19:127-133. 1982-03-24 21:46:47.
A caged population of Anopheles gambiae was allowed to breed continuously and samples of the progeny were tested for susceptibility to Plasmodium yoelii nigeriensis. Males of a strain partially refractory to this parasite were released into the population for an 18-wk period. The susceptibility of the population declined from 100% to about 50% and remained at that level for several months after releases were terminated. Separate experiments showed that the fitness of the adult males and larvae of the refractory strain was much less than that of the susceptible caged strain. The observed change in the susceptibility of the caged population was compared with the expectations on various assumptions about the relative fitness of the refractory and susceptible strains. It appears that initially the efficiency of the replacement process was considerably reduced because of poor fitness of the refractory strain. Once the refractoriness genes were in the caged population, however, they were able to recombine with the genes causing poor fitness and the latter could be eliminated by natural selection, leaving a considerable degree of refractoriness in the population. The results are discussed in relation to the possibility of vector control by the release of males from a refractory strain and with particular reference to the advantages and disadvantages of the use of a negatively heterotic system to assist the replacement process and the release of both sexes.
Sex ratio distortion caused by meiotic drive in a mosquito Culex pipiens
4485Sweeny, TLB, A. R., Genetics, 88:427-446. 1978-01-03 00:00:00.
A genetic factor, distorter (d), has been discovered that upsets the normal sex ratio of 1 : 1 and results in a large excess of males in Culex pipiens. The effect can be explained by a sex-linked, recessive gene. Males homozygous for the gene (Md/md) produce few female offspring; the effect is not due to postzygotic mortality. During the first meiotic division in spermatogenesis, the shortest chromosome pair, which, according to JOST and LAVEN (1971), is associated with sex determination, can be seen to be abnormal. In a high proportion of spermatocysts, one of the dyads of the shortest bivalent fragments, and the pieces are distributed irregularly to the daughter cells. It is believed that the female-determining chromosomes fragment. This would give rise to an excess of male-determining sperm. The possible usefulness of this factor for control or for experimental purposes is discussed.
Resistance to meiotic drive at MD locus in an Indian wild population of Aedes aegypti
4488Suguna, SGW, R. J.; Curtis, C. F.; Whitelaw, A.; Kazmi, S. J., Genetical Research, 29:123-132. 1977-01-06 00:00:00.
Females from an Indian wild population of Aedes aegypti were crossed to males carrying the sex ratio distorter factor MB which shows meiotic drive. Progenies from ¥1 males were tested for sex ratio distortion, i.e. the chromosomes from the wild females were screened for their resistance to the action of M°. The distribution of sex ratio in the progenies of different ¥1 males indicated a polymorphism in the wild population for resistant and sensitive variants of the X chromosome. Seven discrete categories of X appear to exist, associated with sex ratios ranging from 50 % $ to less than 1'25 % $. The overall level of resistance varied slightly but significantly in different parts of a town. The results are discussed in relation to the use of sex ratio distortion for genetic control of mosquitoes.
Genetic control of insect populations: I. Cage studies of chromosome replacement by compound autosomes in Drosophila melanogaste
6297M. Fitz-Earle, D. G. Holm and D. T. Suzuki, Genetics, 74:461-475. 1973-07-08 19:53:27.
A genetic method for insect control was evaluated using the test organism, Drosophila melanogaster. The technique involved the displacement under a system of continuous reproduction, of standard strains by those carrying compound autosomes. The eradication of the replacements could subsequently be achieved through the use of temperature-sensitive lethal mutations.—While certain compound autosome strains failed to displace standards in population cages, even at the initial release ratio of 25:1, others were highly successful. Indeed, for some strains when the ratio of compounds to standards was as low as 9:1, the population rapidly went to fixation in favor of the compound line.—Hatchability was found to be an insufficient index of fitness to estimate the initial ratios of compounds to standards that would guarantee fixation of the former. Differences in other fitness components, such as development time, were detected that could seriously modify displacement, especially with continuous overlapping generations. The importance of examining the fitness of various compound lines and selecting the most competitive in cages, prior to field tests, cannot be overemphasized.
Changing population structure through the use of compound chromosomes
6295D. Childress, Genetics, 72:183-186. 1972-09-08 19:50:49.
Theoretical calculations and population cage data are presented to illustrate the use of compound chromosomes to change the genetic structure of insect populations.
Chromosome rearrangements for the control of insect pests
6293G. G. Foster, M. J. Whitten, T. Prout and R. Gill, Science, 176:875-880. 1972-05-26 19:48:27.
Over several years some biologists have been interested in the possibilities of employing genetic techniques in the control of insect pests. One idea has been to introduce in the natural population genotypes which could subsequently facilitate control, or which might render the pest innocuous. An- other idea that followed from the success of the .'sterile male" technique was to release genotypes with chromosomal aberrations whose subsequent segregation would result in sterility effects damaging to the population. Whitten (I) suggested combining these two ideas in one operation: in its simplest form the desired genotype would be obtained by incorporating the required genes in a chromosomal translocation. This would then be released as a homozygote in excess of the intrinsic unstable equilibrium which would result from the semisterility of the translocation heterozygote. The translocation producing the desired genotype would then autonomously become fixed while the genotype at the same time would produce sterile progeny in the early stages of the process. Thus we have the concept of a genetic transporting mechanism and a desired genotype to be transported, with the additional benefit of a transport device that might itself have transient damaging effects.
Insect control by genetic manipulation of natural populations
6300M. J. Whitten, Science, 171:682. 1971-02-19 19:57:36.
The possible use of chromosome rearrangements is considered as a means for introducing genes into insect populations for their own control. The release of laboratory-constructed strains differing from the field population for a number of chromosome interchanges should create an unstable situation leading to the rapid replacement of the field population. This replacement should allow introduction of genes for insecticide susceptibility, cold sensitivity, or the like. The process would produce sterile hybrids while the genetic displacement occurs which itself will contribute to a reduction in pest numbers.
Applications of genetic technology to mosquito rearing
6098G. B. Craig, Bulletin of the World Health Organization, 29:89-97. 1963-01-02 16:40:36.
Since the development of insecticide-resistance and the consequent partial failure of the chemical approach to the control of disease vectors, interest in the biological approach has re-awakened. An aspect of the latter approach that is of great current interest is " autocidal control "-that is, the use of insects for their own destruction. This paper discusses the various ways in which genetic mechanisms can be used to bring about the destruction of harmful insects, with special reference to those of medical importance. The author considers that the prospects for the genetic control of vector species are good, but stresses that before genetic methods can be applied on a field scale certain requirements must be met. For example, genetic technology must be expanded, a firm background of genetic knowledge of vector species must be built up, a great deal more information about vector ecology, particularly population dynamics, must be acquired, and techniques for the mass production of vector insects under controlled conditions must be developed.
Inherited male-producing factor in Aedes aegypti
6096G. B. Craig, W. A. Hickey and R. C. Vandehey, Science, 132:1887-1889. 1960-12-23 14:59:02.
An inherited factor causes a predominance of males in certain strains and in progeny of single pairs of Aedes aegypti L. This factor appears to be transmitted only by males and is not due to differential mortality, at least in postgametic stages. Mass release of male-producing males might be used in control operations.
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