Keywords: Gene drive
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.
Optimal spatial release strategies for confined gene drives and Wolbachia
35488Ziye Wang, Jackson Champer, bioRxiv, 2026-03-06 10:19:13.
Gene drives are genetic elements that can rapidly spread through populations, offering potential solutions for controlling disease vectors and pests. In some scenarios, it is necessary to utilize drives that can be confined to only target populations. The success of these threshold-dependent gene drives, which require a minimum local frequency to establish, depends critically on the spatial strategy used for introduction. Here, we use a reaction-diffusion model to systematically identify optimal release patterns that maximize the per-capita efficiency for four distinct gene drive designs as well as use of Wolbachia bacteria, which spread similarly to frequency-dependent gene drives. We find that the most efficient release strategy is highly dynamic, transitioning from a broad "everywhere" release for short timeframes to a "multiple-ring" pattern for intermediate times, and finally to a focused "center" release for longer timeframes. These timeframes depend on the specific type of drive, with more powerful variants transitioning more quickly to center releases. Our results demonstrate that these optimized, variable release strategies can be substantially more effective than simple uniform releases. This study provides a quantitative framework for designing effective gene drive implementations, highlighting that a carefully planned spatial strategy is essential for maximizing impact, making optimal use of available resources.
Comparison of single-cell sequencing technologies for allele-specific expression analysis in rabbit spermatids
35482Elena Smertina, Madi Rutherford, Brendan Hosking, et al., Genomics, 2026-03-05 08:26:37.
Gene drives are transmission distorters that can transmit specific alleles to >90% of the progeny, e.g., the naturally occurring t-haplotype in mice. For invasive pest species, there is interest in co-opting naturally occurring gene drives. It is unknown whether similar natural gene drives exist in the European rabbit, one of the most detrimental pest species in Australia. Here, we analysed the allele-specific expression (ASE) in rabbit spermatids to identify candidate genes for future investigation in genetic biocontrol applications. We utilised short-read and long-read technologies and performed a comparative analysis. Illumina sequencing was deemed unsuitable, whereas both long-read sequencing platforms demonstrated a similar performance. The SPINK2 gene that plays an important role in fertility, consistently showed ASE towards one of the alleles in all samples. Furthermore, two kinases were found to display a bimodal allele expression. Future work is warranted to assess suitability of these genes for genetic biocontrol applications.
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.
Stochastic dynamics at the back of a gene drive eradication wave
35468Léna Kläy, Léo Girardin, Florence Débarre, Vincent Calvez, Theoretical Population Biology, 168:44-64. 2026-02-24 14:22:40.
Gene drive alleles bias their own inheritance to offspring. They can fix in a wild-type population in spite of a fitness cost, and even lead to the eradication of the target population if the fitness cost is high. However, this outcome may be prevented or delayed if areas previously cleared by the drive are recolonised by wild-type individuals. Here, we investigate the conditions under which these stochastic wild-type recolonisation events are likely and when they are unlikely to occur in one spatial dimension. More precisely, we examine the conditions ensuring that the last individual carrying a wild-type allele is surrounded by a large enough number of drive homozygous individuals, resulting in a very low chance of wild-type recolonisation. To do so, we make a deterministic approximation of the distribution of drive alleles within the wave, and we split the distribution of wild-type alleles into a deterministic part and a stochastic part. Our analytical and numerical results suggest that the probability of wild-type recolonisation events increases with lower fitness of drive individuals and with smaller local carrying capacity. Numerical simulations show that these results extend to two spatial dimensions. The role of the migration rate however, is less clear but has a lower impact. We further demonstrate that, in the event of wild-type recolonisation, the probability of subsequent drive reinvasion decreases with smaller values of the intrinsic growth rate of the population. Overall, our study paves the way for further analysis of wild-type recolonisation at the back of eradication travelling waves.
Spatial confinement of gene drives: Assessing risk of failure using global sensitivity analysis
35459Cole D. Butler, Alun L. Lloyd, bioRxiv, 2026-02-19 09:59:30.
Gene drives allow pest populations to be genetically modified to reduce their harm on agriculture and human health. The genetic modification, or payload, spreads within a target population at rates exceeding normal Mendelian inheritance. While gene drives have demonstrated immense potential in laboratory populations, they present unique challenges. Foremost among these challenges is spatial confinement, or ensuring that the payload remains confined to target populations. However, there is an inherent tension between gene drive spread and spatial confinement: increasing the spreading efficiency of a gene drive increases the risk of escape, while engineering confinement mechanisms increases the risk of gene drive extinction. In this work, we explore spatial outcomes in gene drives designed for spatial confinement and the dependence of these outcomes on target organism dispersal and payload fitness cost. We use a stochastic spatial model to compute the probability of failure for each gene drive, and use techniques from global sensitivity analysis to quantify the contribution of dispersal and fitness cost to variance in gene drive performance. Our findings reveal how spatial outcomes are affected by key parameters, and how this sensitivity varies tremendously between different gene drives. These spatial properties can be used to classify gene drive behavior and are useful to determine suitability for a particular application.
Upper bound on the mutational burden imposed by a CRISPR-Cas9 gene-drive element
35463Michael S Overton, Sean E Guy, Xingsen Chen, et al., G3 Genes|Genomes|Genetics, 2026-02-18 10:08:37.
Homing-based CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, with applications from disease eradication to species conservation. However, Cas9 alone and in a complex with guide RNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to unintended loss-of-heterozygosity (LOH) events. These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To measure how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeast Saccharomyces cerevisiae. We found no detectable effects on the genome-wide rates of mutations or LOH events. Our power calculations suggest that CCGD or Cas9 affect these rates by less than 30%, which is much less than natural variation for these traits in yeast. A more detailed examination shows that CCGD or Cas9 may alter the lengths and genomic distributions of LOH events, but the statistical support for these effects is weak. Thus, our results demonstrate that CCGDs impose at most a weak additional mutational burden in the yeast model. Although mutagenic effects of gene drives need to be further evaluated in other systems, our results add credence to the proposition that the evolutionary risks posed by well-designed gene drives may be acceptable.
Biocontrol practitioners’ perspectives on emerging genetic-based technologies for weed management
35412Rafter, M.A., Kumaran, N., Brookes, D.R. et al., BioControl, 2026-01-31 16:43:25.
Weed biocontrol researchers have been at the forefront of developing management solutions for invasive weeds for over 100 years and have a unique perspective to offer on the emerging field of genetic-based technologies such as gene drive and RNAi. As part of the XVI International Symposium on Biological Control of Weeds in May 2023 we conducted a focus group discussion workshop to explore biocontrol practitioners’ perspectives related to: (1) Genetic-based control technologies, and the factors influencing support (or not) for their application to weed management, especially weed biocontrol, (2) perceived opportunities to apply genetic-based control tools to enhance or complement weed biocontrol, focusing on whether/how genetic tools can be applied to fundamentally change the practice of weed biocontrol, and (3) genetic-based control in weed management and how it can operate within the Access and Benefit Sharing regulatory landscape. We analyse the perspectives of biocontrol scientists from the workshop and discuss the prospects and challenges of integrating novel genetic-based control tools with weed biocontrol.
Microhomology-mediated end joining is the predominant form of DNA repair in the mosquito Aedes aegypti with implications for gene editing, gene drive, and transgene removal
35375Joseph S Romanowski, Kevin M Myles, Zach N Adelman, Nucleic Acids Research, 54. 2026-01-20 16:30:25.
Programmable site-specific nucleases have revolutionized the field of genetics, and in the field of mosquito vector control, gene editing by these tools has inspired a new wave of population control approaches that aim to prevent disease transmission. Little is known of how DNA repair is prioritized in mosquitoes, which diverged from the nearest model system (Drosophila) by >200 million years, despite site-specific gene editing now being commonplace. Here, we report a scalable, high-throughput platform for studying DNA double-stranded DNA break (DSB) repair in mosquitoes by delivering CRISPR/Cas9, I-SceI, or other nucleases to Aedes aegypti embryos, capable of measuring single-strand annealing (SSA), non-homologous end joining, and microhomology-mediated end-joining (MMEJ) repair outcomes. We find CRISPR/Cas9 can induce deletions of up to 8.6 kb through SSA repair and is tolerant of resection distances of 3.5 kb. Indel events were insensitive to lig4 knockouts, and across 20 synthetic guide RNAs (sgRNAs) representing 5 locations in 2 transgenic strains were almost exclusively attributed to MMEJ repair, establishing MMEJ as the dominant form of repair in A. aegypti at CRISPR/Cas9 DSBs. This information is critical to our understanding of how DNA repair shapes processes required for genetic control strategies involving gene drive action/resistance as well as transgene stability.
The Genomic Arms Race in Mosquito-Borne Diseases: Integrating Entomopathogenic Fungi, Gene Drive, and Symbiont Technologies for Sustainable Vector Control
35503Rajendran Yamini, Pagalahalli Sankaran Shanmugam, Marimuthu Murugan, et al., J Pure Appl Microbiol., 20:53-65. 2026-01-20 09:32:56.
Mosquito-borne diseases such as malaria, dengue, Zika, chikungunya, and lymphatic filariasis continue to impose enormous health and economic burdens worldwide. The traditional reliance on chemical insecticides has been undermined by the rapid evolution of resistance, ecological concerns, and declining efficacy. Next-generation biocontrol strategies are framed within the concept of a “genomic arms race” between mosquitoes, pathogens, and microbial agents. Entomopathogenic fungi are eco-friendly bioinsecticides with demonstrated efficacy in laboratory, semi-field, and transgenic applications. Symbiont-based approaches, particularly those involving Wolbachia, have been evaluated for their ability to reduce vector competence and spread through populations. Parallel advances in CRISPR-based gene drive technologies have provided transformative tools for population suppression and modification, although their deployment is limited by ethical, ecological, and regulatory concerns. An integrated vector management (IVM) framework combining fungi, gene drives, and symbiont-based tools is proposed as the most promising approach for sustainable mosquito management. This multipronged strategy has the potential to reduce disease transmission, delay resistance development, and minimize ecological disruption, paving the way for resilient, eco-friendly solutions against vector-borne diseases.
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.
Research Advances and Challenges of Gene Drive Technology in Mosquito-Borne Disease Control
35363Yun Jiaqi, Ma Qin, Wang Guandong, et al., Laboratory Animal and Comparative Medicine, 45:773-783. 2026-01-14 12:01:39.
Mosquito-borne diseases (such as malaria, dengue fever, Zika virus disease, and Chikungunya) pose major threats to global public health, while traditional control methods based on chemical pesticides face severe challenges including enhanced drug resistance in vector mosquitoes and environmental pollution. Genetic control strategies have become high-potential alternative solutions for mosquito control due to their species specificity and environmental friendliness. Gene drive technology uses gene editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) to enable specific genes to efficiently spread in target mosquito populations through "super-Mendelian inheritance", offering a revolutionary strategy for the prevention and control of mosquito-borne diseases. This review systematically summarizes key advances, core challenges, and response strategies of gene drive technology in this field. Research advances: (1) In Anopheles malaria vectors, population suppression drives targeting sex determination genes or female reproductive genes can cause female sterility or skewed sex ratios to achieve population suppression. Population replacement gene drive strategies targeting host genes associated with Plasmodium infection or delivering anti-Plasmodium effector molecules in Anopheles can effectively block pathogen transmission. (2) In Aedes mosquito vectors of arboviruses, targeting female flight-essential genes achieves population suppression, and coupling of antiviral effector systems with drive elements is explored. Optimized split gene drive strategies demonstrate high cutting and recombination efficiency, and models predict safe and controllable spread of disease-resistance traits. (3) In Culex mosquitoes transmitting lymphatic filariasis, homology drive elements are integrated into two genes involved in the eye pigment synthesis pathway, allowing clear visualization of gene drive efficiency through eye color. Core Challenges: technological challenges include low homologous recombination repair efficiency, non-homologous end joining repair causing resistance allele generation, CRISPR/Cas9 off-target effects, and species adaptation differences. Ecological and safety challenges involve gene pool pollution caused by accidental spread of drive elements, potential ecological balance impacts, and long-term irreversible risks. Response strategies and prospects: employing multiplex guide RNA (gRNA) targeting strategies to enhance drive stability and combat potential resistance. Developing reversible designs such as synthetic resistance, reversal drives, and immunizing reversal drives as "genetic brakes". Establishing long-term ecological monitoring systems and mathematical modeling for risk assessment. Exploring "environmentally responsive drives" to enhance controllability. Future research should continuously optimize drive efficiency and specificity, deepen ecological risk evaluation, strengthen international cooperation, and promote ethical consensus and regulatory framework construction, with the aim of making gene drive technology a sustainable prevention and control strategy to address the global health challenge of mosquito-borne diseases under the premise of safety and controllability.
Exploratory conversations with biodiversity-oriented civil society groups on the potential applications of gene drive-modified mosquitoes for malaria control in Tanzania
35354Finda, M.F., Sambo, M., Malika, G. et al., Transgenic Res, 35. 2026-01-13 09:53:50.
Gene drive-modified mosquitoes (GDMMs) are gaining attention as sustainable tools to complement existing malaria control strategies. Their ability to self-propagate and spread through wild mosquito populations offers the promise of low-cost, long-lasting impact, but also raises ecological, ethical, and governance concerns. In this evolving debate, civil society organizations (CSOs) are pivotal actors in shaping dialogue, representing community concerns, and influencing policy decisions. This study examined the perspectives and recommendations of biodiversity-oriented CSOs on the governance, testing, and potential application of GDMMs for malaria control in Tanzania. An exploratory qualitative design was employed, involving eight in-depth interviews, one focus group discussion, and three large group discussions with representatives from ten biodiversity-focused CSOs in Tanzania. Participants were selected purposively based on prior involvement in national or regional dialogues related to biotechnology; and the discussions focused on concerns, uncertainties and needs associated with testing and potential use of GDMMs for malaria control, as well as the balance of prospective benefits against long-term environmental risks. Transcripts were analyzed thematically using NVivo 12 Plus. Participants expressed cautious support for research on GDMMs for malaria control but raised concerns about scientific uncertainty, limited local expertise, inadequate transparency, potential transboundary effects and technological dependency. They emphasized the importance of generating robust, context-specific evidence before considering any environmental releases of gene drives; and highlighted concerns over inadequate accountability, particularly the lack of clarity on who would assume responsibility if adverse outcomes arise. They also advocated for early, inclusive, transparent, and continuous engagement with both target communities and the broader public. Lastly, to ensure objective and impartial oversight, they recommended development of local expertise that is independent of technology developers and sponsors. The CSOs’ perspectives were diverse but broadly aligned with the precautionary principle, calling for preventive action amid uncertainty, clear accountability, and the pursuit of safer alternatives. Although many expressed serious reservations about gene drive mosquitoes, there was a shared recognition that research on the technology is necessary, provided it is conducted under controlled, transparent, and auditable conditions. Overall, these exploratory discussions underscored the need for: (i) balanced dialogue between advocates and skeptics, (ii) robust ethical and regulatory frameworks covering the full life cycle of the technology, (iii) sustained community and stakeholder engagement from the early stages of research and development, (iv) enhancements of in-country capacity, and (v) national sovereignty in decision-making regarding GDMMs. Demonstrating and effectively communicating these elements will be as critical as ensuring their existence.
The role of toxin/antidote genes in the maintenance and evolution of accessory chromosomes in Fusarium
35333Linnea Sandell, Adrian Forsythe, Anna Mirandola, et al., Genetics, 231. 2025-12-31 14:56:39.
The genomic diversity of many fungal species is augmented by accessory chromosomes, which are variably present in individual strains. These genomic regions evolve rapidly, accumulating genes important in pathogenicity but also harbor a significant number of transposable elements. This duality suggests a trade-off: accessory chromosomes provide infection-related benefits while otherwise being deleterious due to their highly repetitive nature and contributions to genomic instability. Despite this, accessory chromosomes often appear to be stably maintained even when strains are grown on media, with no plant host. Previously, we had observed that genes homologous to meiotic drive toxin/antidote proteins from Podospora anserina (Spoks) are abundant on accessory chromosomes in various Fusarium species. Using a functionality screen in yeast, we demonstrate that some of these homologs have active toxin and antidote properties. We propose that these selfish genes could maintain accessory chromosomes during vegetative growth and may influence their spread via parasexual cycles. Finally, as Spok genes are found on the newly described transposable element superfamily Starships, we also present a model for how these transposable elements could play a role in forming accessory chromosomes and regions. These results illuminate a mysterious facet of fungal biology, a key step towards describing the origin, spread, and maintenance of pathogenicity in many fungal species.
A target product profile for a rapid diagnostic test to monitor mosquito gene drive presence and frequency
35345Prateek Verma, Sebald Verkuijl, Calvin K. Yee, et al., bioRxiv, 2025-12-18 10:23:36.
Malaria remains a major global health challenge, with over 263 million cases and nearly 600,000 deaths reported in 2023, the majority in sub-Saharan Africa. While conventional interventions such as insecticide-treated nets, indoor residual spraying and antimalarial drugs have reduced transmission, progress has stalled due to the limitations of these interventions and the emergence of resistance. Gene drive-modified mosquitoes represent a promising, potentially transformative vector control strategy, capable of spreading malaria-refractory traits or suppressing mosquito populations. Successful field deployment will depend upon monitoring systems to track the presence and frequency of gene drive constructs as they spread and persist. Current molecular surveillance techniques, though effective, are resource-intensive and reliant on laboratory infrastructure and technical competencies. Here, we make the case for a near-universal and low-cost rapid diagnostic test (RDT) designed to detect gene drive mosquitoes in the field, to complement existing surveillance infrastructure. Two use cases are outlined: i) to detect the presence of the drive construct in a new population, and ii) to provide an estimate of drive frequency prior to more accurate laboratory-based measurements. We provide a target product profile for the RDT outlining minimally essential and ideal characteristics, including test procedures, sensitivity, specificity, usability by a range of stakeholders in field settings, and compatibility with pooled testing of mosquito samples. An RDT for gene drive construct detection would support community access and participation in monitoring, enhance regulatory oversight, and promote transparency in field trials, thereby facilitating responsible deployment of gene drive-based malaria interventions.
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.
Gene drives, species complexes, and the risks of collateral damage
35296C. Boëte, Proc. Natl. Acad. Sci., 122. 2025-11-09 18:26:26.
The development of engineered gene drive systems continues to garner significant interest. Theoretically, these systems could spread traits in a target species (an approach known as population replacement) or eliminate a population within a few generations (population suppression). Some researchers have promoted this disruptive technology for potential applications ranging from public health (e.g., malaria control) to conservation (e.g., protection of endangered species, elimination of invasive ones) to agriculture (e.g., pest control). But in the case of a gene drive intended to target a specific species, the risk of affecting non-target species must be taken into account, and researchers must strive to minimize collateral damage. Hybridization between a target and a non-target species could result in unintended gene flow, as could the horizontal transfer of the gene drive cassette (1). While some researchers have proposed the “Target Species Complex” (TSC) framework to account for off-target effects, the concept is unlikely to provide a safeguard. Rather, it risks reframing collateral impacts as intentional outcomes, narrowing, rather than broadening, the scope of ecological and regulatory considerations. Researchers must therefore make sure to incorporate risk assessments that take into account the effects on numerous species and make a concerted effort to understand the downstream effects.
Variants in Cas9 and nanos regulatory elements modulate activity and reduce resistance allele formation in homing gene drive
35294Ruizhi Zhou, Jie Du, Nicky R. Faber, Jackson Champer, bioRxiv, 2025-11-09 18:15:12.
Gene drive is a novel approach for controlling vector borne disease via either population modification or suppression. Even with high efficiency, though, overall drive performance can be reduced by somatic Cas9 expression and by maternal deposition of Cas9, leading to resistance allele formation. The nanos promoter for Cas9 shows very little leaky somatic expression, but it causes high rates of embryo resistance allele formation in Drosophila melanogaster. By truncating the promoter, we reduced rates of embryo resistance to undetectable levels, but germline cutting in females decreased by over half. Germline cutting and successful drive conversion was eventually lost when only the 5′ UTR was present, though males still retained moderate germline drive efficiency. Several additional methods were tested to improve performance, including additional suppressor elements to the 3′ UTR and introns to increase expression level. The most successful of these was the addition of a second nuclear localization signal, which substantially increased activity when coupled with a full-length or truncated nanos promoter. Overall, these experiments show the potential to modulate Cas9 regulatory elements to achieve desired expression for gene drive applications, while also showcasing the difficulty of obtaining an optimal activity profile.
The nanosd integral gene drive enables population modification of the malaria vector Anopheles gambiae
35269Pei-Shi Yen, Sebald A N R Verkuijl, Paolo Capriotti, et al., G3 Genes|Genomes|Genetics, 2025-11-02 17:38:52.
The modification of mosquito populations at scale through CRISPR-Cas9-mediated homing gene drives is a promising route for malaria vector control. Integral gene drives (IGDs) are designed to utilise the regulatory sequences of endogenous genes to reduce the size of the modification required for nuclease and effector expression. In this study, we describe the creation and characterisation of the nanosd IGD, which targets and is inserted into the nanos gene of the malaria vector Anopheles gambiae, and show that it achieves high rates of gene drive (98.4% in females, 99.5% in males). We find that homozygous nanosd females but not males show impaired fecundity and exhibit variable degrees of ovary underdevelopment. Transcriptomic analysis of ovaries points to decreased transcript levels of the nanos gene when harbouring Cas9 and changes to other fertility-related genes. As a minimal genetic modification, nanosd does not induce widespread transcriptomic perturbations that would affect vector competence, and we show that its susceptibility to Plasmodium spp. and O’nyong nyong virus infection remains similar to wild-type mosquitoes. Importantly, we find that nanosd propagates efficiently in caged mosquito populations and is maintained as a source of Cas9 after the emergence of drive-resistant alleles, whilst also mobilising a non-autonomous antiparasitic effector modification. The nanosd gene drive shows promise as a genetic tool for malaria vector control via population modification, and we outline steps towards its further optimisation.
Highlight: Self-limiting gene drive suppresses malaria mosquitoes
35263Gorm Palmgren, CRISPR Medicine News, 2025-11-02 17:22:29.
Malaria claimed over 600,000 lives in 2022, with Anopheles gambiae serving as one of the most efficient vectors in sub-Saharan Africa, where approximately 96% of malaria deaths occur. The emergence of insecticide resistance threatens progress in disease control, prompting the development of genetic strategies to address it. CRISPR-homing gene drives have emerged as the most studied self-sustaining approaches, whilst various self-limiting methods that require repeated releases continue to be explored. The research team developed a system, termed Male-Drive Female-Sterile (MDFS), that exploits CRISPR-Cas9 to simultaneously perform two distinct functions (see Figure 1). The genetic construct contains an eCFP fluorescent marker, a Cas9 endonuclease under the control of the germline vasa2 promoter, and a guide RNA targeting the female-specific exon 5 of the doublesex gene. The construct was integrated into the doublesex locus at the intron 4–exon 5 boundary using recombinase-mediated cassette exchange.
Exploring experts’ uncertainties about gene drive technology for agricultural pest control in the U.S.: a qualitative study to inform innovation and decision-making
35241Barry, N., Barnhill, S.K. & Johnson, B.B., Environment Systems and Decisions, 45. 2025-10-15 08:34:10.
As experts consider what it might look like for gene drives to manage agricultural pests, there remain several uncertainties across a broad range of issues, including technical, ecological, regulatory, and social implications. Drawing on 25 expert interviews, we parse out these uncertainties and the potential for Adaptive Management to help guide development, deployment, and governance of gene drives for invasive agricultural pest management. Adaptive Management emerged specifically to attend to uncertainties in complex social-ecological systems, prescribing collective learning and responsiveness to stakeholder feedback to effectively reach management goals. Thus, Adaptive Management provides clear direction on how to account for and make decisions in the face of considerable uncertainties surrounding these gene drive tools. We also give some attention to the ways in which the uncertainties that are specific to agricultural applications are somewhat distinct from or consistent with global discourse around gene drive development across sectors.
Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae
35231Smidler, A.L., Marrogi, E.A., Scott, S. et al., Scientific Reports, 15. 2025-10-09 10:19:39.
Gene drives are selfish genetic elements which promise to be powerful tools in the fight against vector-borne diseases such as malaria. We previously proposed population replacement gene drives designed to better withstand the evolution of resistance by homing through haplolethal loci. Because most mutations in the wild-type allele that would otherwise confer resistance are lethal, only successful drive homing and functional r1 alleles permits the cell to survive. Here we outline the development and characterization of two ΦC31-Recombination mediated cassette exchange gene drive docking lines with these features in Anopheles gambiae, a first step towards construction of robust gene drives in this important malaria vector. We outline adaption of the technique HACK (Homology Assisted CRISPR knockin) to knock-in two docking site sequences into a paired putative haplolethal-haplosufficient (Ribosome–Proteasome) locus, and confirm that these docking lines permit insertion of drive-relevant transgenes. We report the first anopheline proteasome knockouts, and identify ribosome mutants in the process reveal a major lethality and infertility hurdle that such designs must overcome to develop robust drives in the future. Although we do not achieve drive, this work provides a new tool for constructing future evolution-robust drive systems and reveals critical challenges that must be overcome for development of future gene drives designed to target haplolethal loci in anophelines and, potentially, other metazoans.
Finding the perfect promoter: Correlating single-cell transcriptome data with gene drive performance
35228Yingke Wu, Yunchen Xia, Ziyin Yao, et al., bioRxiv, 2025-10-09 10:07:12.
Gene drive can control pathogen transmission or suppress vector populations by spreading drive alleles with super-Mendelian inheritance. CRISPR homing drive currently represents the most powerful type, and regulating Cas9 expression with specific promoters has been effective for improving drive performance. However, selecting these is often a major challenge. Here, we evaluated 35 Cas9 constructs driven by distinct promoters in different gene drive systems and identified associations between drive performance and single-cell RNA expression patterns of the promoter-associated genes. Our results indicate that higher drive conversion is significantly associated with elevated expression of the promoter-associated gene in the respective reproductive cells, but embryo resistance allele formation correlates with excessive female germline expression. For males, early germline expression produces superior performance. Thus, we find that optimal drive performance requires restricting Cas9 expression to a tight quantitative and spatiotemporal window. In addition, found that in situ integrated rhino-Cas9 constructs significantly reduce somatic expression, underscoring the importance of genomic locus. On the basis of these results, we propose criteria for selecting promoters, providing a theoretical rationale and practical guidance for optimization of promoter elements in homing gene drive systems.
Systemic tumor-targeting gene drive vectors proactively eliminate drug resistance in solid tumors
35223Scott M Leighow, Michael Hemann, Justin Robert Pritchard, bioRxiv, 2025-10-07 13:57:44.
While targeted therapies have revolutionized cancer treatment, drug resistance remains a major barrier to their curative potential. We recently demonstrated biological proof-of-concept for selection gene drive circuits, a technology that overwrites disease evolution to proactively eliminate resistance in vivo, but translation requires a delivery method compatible with disseminated metastatic disease. Now, we demonstrate a clinically feasible delivery solution with novel tumor-targeting lentiviral vectors that selectively install these therapeutic circuits in tumor cells in situ. Systemic administration of these vectors demonstrated durable elimination of visible tumor burden and minimal body weight loss, validating the translational potential of a new class of genetic medicines for long-term control of resistance in cancer.
Engineered Gene Drives
35221Convention on Biological Diversity, 2025-10-05 20:11:01.
This page is dedicated to living modified organisms containing engineered gene drives and was developed further to decision CP-10/10 of the Conference of the Parties serving as a meeting of the Parties to the Cartagena Protocol on Biosafety (COP-MOP).
Apprehension of Technosciences and Initiation to Education for Uncertainty: Case of Gene Drive
35163Hayet Saoudi and Hanen Bouamoud, Qualitative Approaches to Pedagogical Engineering, 2025-09-22 15:39:06.
This research falls within the framework of education about uncertainty. The authors focused on one of the technosciences, namely genetic engineering, and treated it as a ‘socially acute issue'. The research involved a group of Tunisian third-year students in life and earth sciences. They are a group of potential future teachers. They set up a three-phase experiment. The first phase consisted of a pre-test quiz, aimed at assessing the students' scientific knowledge and the forms of uncertainty they mobilised. The second phase consisted of watching videos on technoscience and genes. The third phase consisted of a post-test quiz designed to monitor changes in the quality of the scientific knowledge required and to highlight the forms of uncertainty used. For the analysis, the authors used analytical grids to characterise the quality of the scientific knowledge and the forms of uncertainty involved. The results show that integrating socially current issues has a significant effect on education about uncertainty and on the acquisition of scientific knowledge.
Advances in population-based interventions to control falciparum malaria
35153Samuel E Glossop, Thomas J Peto, Bipin Adhikari, Transactions of The Royal Society of Tropical Medicine and Hygiene, 2025-09-22 10:26:25.
Malaria is a complex disease and transmission can be prevented in multiple ways. A range of interventions to achieve this became widely available from the year 2000, and cases continually declined, but progress has plateaued since 2015. This review aims to cover the population-level prevention strategies responsible for this and those that could continue this progress, focusing on how they can be successfully integrated. Insecticide-treated nets (ITNs) made the most substantial contribution to reducing malaria mortality, but their distribution, access and use remains suboptimal while development of insecticide resistance requires continuous adaptation. Chemoprevention provides protections to tens of millions of people, primarily children in sub-Saharan Africa, but is also threatened by the emergence and spread of drug resistance. These strategies may have reached a point of saturation for reducing morbidity and mortality, thus calling for innovative developments to build upon more basic approaches such as accurate early diagnosis, appropriate treatment and improved housing. The R21/Matrix-M vaccine is a significant improvement over the RTS,S/AS01 vaccine, with greater efficacy, lower cost and scalable mass production. Field trials of current monoclonal antibodies (mAbs) suggest that next-generation mAbs could be a promising tool for seasonal chemoprophylaxis. Furthermore, gene drives may have the potential to eradicate entire populations of malaria-transmitting mosquitoes. A multifaceted approach combining these new strategies with traditional approaches (ITNs and chemoprevention) offers a framework to reinvigorate progress towards malaria elimination.
Experimental demonstration of daisy chain gene drive and modelling of daisy suppression systems
35147Jialiang Guo, Weizhe Chen, Jackson Champer, bioRxiv, 2025-09-22 10:06:58.
CRISPR-based gene drive can address ecological problems by biased inheritance coupled with an effector for either population modification of suppression. However, the potential risk of uncontrolled spread impedes some applications of gene drive. Daisy chain gene drives have received much attention as a potential approach to overcome this problem. They potentially allow the efficient spread of drive elements in a target population, but are ultimately self-limiting. This is achieved by splitting a normal gene drive system into multiple dependent drive elements, where each element can bias the inheritance of another, except one non-driving element. With the successive loss of each chain link, the spread of transgenic elements will slow down and eventually stop. Here, we use modelling to assess the population dynamics of daisy chain drives in both panmictic and continuous space models, focusing on suppression systems. We find that achieving population elimination through a single release of daisy chain gene drives is possible but difficult, with relatively high requirements for drive performance and release size. These effects are substantially amplified in spatial models. We also constructed two configurations of daisy chain gene drives in Drosophila melanogaster as a proof-of-principle. One is a rescue drive for population modification, and the other aims for population suppression by targeting a haplosufficient female fertility gene. These drives all functioned within expectations at moderate efficiency in individual crosses. However, the drive design failed to spread in cage populations because of higher than expected fitness costs. Overall, our study demonstrates that daisy chain systems may be promising candidates for both modification and suppression, but challenges remain in both construction and potential deployment in large regions.
Mosquito gene drive cancellation disrupts Africa’s malaria research
35139Esther Nakkazi, Nature Africa, 2025-09-12 15:46:02.
The abrupt suspension of an anti-malarial gene drive project in Burkina Faso has disrupted plans by scientists in Uganda working on their own modified mosquitoes. The Target Malaria project was put on hold by Burkina Faso’s government in August. Facilities holding genetically modified mosquitoes were sealed, and all samples ordered to be destroyed. Male mosquitoes released in a village were also neutralised with insecticides. A gene drive sees the release of a modified species with the aim of the modification being passed to the next generation, allowing its frequency to increase rapidly in a population. The project’s freeze casts doubt on other programmes across Africa. Jonathan Kayondo, principal investigator at Target Malaria Uganda, said scientists had not anticipated the decision. “It’s surprising, because Burkina Faso scientists had gone through all the regulatory approvals and were given the go-ahead. They were not operating illegally.” For Ugandan researchers, the termination threatens to disrupt timelines, reshape field study plans, increase costs, and denies the opportunity to build on data gathered. Target Malaria is a not-for-profit international research consortium, aiming to develop genetic technologies to reduce populations of malaria-transmitting mosquitoes in Africa. Since 2012, it has operated at the Research Institute in Health Sciences (IRSS) in Bobo Dioulasso, Burkina Faso, with funding from the Gates Foundation. In 20191, the Burkina Faso team had released a small, non-gene-drive strain of genetically modified mosquitoes, whose strains carry useful traits such as reduced fertility. The modifications were not preferentially inherited, and disappear naturally over generations.
Engagement for genetic modification technologies in conservation: For whom, how, and for what ends?
35126Sylvia Nissen, Franca A. Buelow, Riley Taitingfong, Amanda Black, Environmental Science & Policy, 171. 2025-09-09 09:15:42.
Questions of engagement loom large for the use of genetic modification technologies in conservation. As scientific teams rapidly move towards implementing changes that will fundamentally alter entire species, concerns are regularly raised that associated engagement activities are inadequate. It is therefore vital to take stock of recent social research that critically examines how engagement is being enacted: who is engaged and by whom, how and on what terms, and for whom or what those processes serve. Despite a rise in calls for engagement, our review shows emergent gestures towards engagement by developers and regulators lean strongly towards narrow instrumental approaches that reinforce knowledge hierarchies and existing power imbalances. It contributes to engagement practices that are often vague and tokenistic, and focused on one-way education and snapshots of opinion, rather than mutual reciprocity and dialogue. To counter these undercurrents, our review draws attention to the ways social researchers are seeking to reorient engagement for genetic modification towards its more substantive and democratic possibilities, through articulating process, amplifying plurality, and acknowledging contestation.
Governance Landscape of Gene Drive for Malaria
35069GeneConvene Global Collaborative, 2025-08-28 10:24:11.
This infographic presents a hypothetical example of how real governance mechanisms could work to make decisions about gene drive field trials.
Genetic control strategies for population suppression in the Anopheles gambiae complex: a review of current technologies
35055Alekos Simoni, Ignacio Tolosana, Federica Bernardini, Current Opinion in Insect Science, 2025-08-25 20:42:10.
Malaria continues to pose a critical public health threat, with mosquitoes from the Anopheles gambiae complex acting as the main vectors of the disease in sub-Saharan Africa, where approximately 95% of malaria-related deaths occur. Despite significant advancements in vector control, such as insecticide-treated bed nets and indoor spraying, the effectiveness of these interventions is increasingly compromised by various challenges, including rising levels of insecticide and pathogen resistance, mosquito behavioural adaptations, and persistent funding gaps. In this context, genetic vector control strategies have shown considerable promise, primarily based on findings from controlled laboratory studies. This review explores the development of these genetic approaches within the Anopheles gambiae complex and outlines future directions for their advancement and potential integration into malaria control efforts.
Ecology and evolution in gene drive modeling
35060NSF-Simons NITMB, YouTube, 2025-08-25 16:09:18.
Speaker: Gili Greenbaum Title: Ecology and evolution in gene drive modeling This talk was recorded as part of the Modeling and Theory in Population Biology workshop at NITMB. The NSF-Simons National Institute for Theory and Mathematics in Biology (NITMB) aims to integrate the disciplines of mathematics and biology in order to transform the practice of biological research and to inspire new mathematical discoveries. NITMB is a partnership between Northwestern University and the University of Chicago. It is funded by the National Science Foundation DMS-2235451 and the Simons Foundations MP-TMPS-00005320. The mission of the NITMB is to create a nationwide collaborative research community that will generate new mathematical results and uncover the “rules of life” through theories, data-informed mathematical models, and computational and statistical tools. The NITMB leverages close collaborations between experimentalists and theorists to synergize discovery. The fundamental research done by NITMB will stimulate advances in areas as diverse as the environment, medicine, and technology development. NITMB members and visitors share space in downtown Chicago that is readily accessible to collaborators across the U.S. and the world. NITMB uses an interlocking set of strategies and initiatives aimed at broad impacts for the mathematical and biological research communities. Targeted research bringing together mathematicians and biologists to collaborate and train the next generation of interdisciplinary scientists. Scientific long programs, workshops, and conferences enhancing collaboration between mathematics and biology. An innovative research program organized around five interrelated themes, selected because they reflect key capabilities of biological systems and interconnect with open mathematical problems.
RESEARCH GROUP PUSHES GENE DRIVE TECHNOLOGY TO END MALARIA IN AFRICA || NEWS UPDATE
35049IDEA TV, YouTube, 2025-08-24 18:23:33.
Tanzania’s bold step toward malaria elimination
35079Guardian Correspondent, IPP Media, 2025-08-20 12:44:23.
It is both mind-boggling and frustrating that an insect with an average lifespan of just two weeks can cause so much sickness and even deaths. Today, on World Mosquito Day, 20th August, the Ifakara Health Institute (IHI) honours Sir Ronald Ross, whose landmark discovery in 1897 confirmed that mosquitoes transmit malaria. His finding not only transformed medical science but also highlighted the profound impact mosquitoes have on public health. For more than a century, his discovery—made while serving with the Indian Medical Services—has continued to remind the world that defeating malaria requires a deep understanding of parasites and efficient mosquito vectors in order to make a real impact in preventing the disease. Globally, vector control has been instrumental in saving millions of lives, mainly through Long-lasting Insecticidal Nets (LLINs) and Indoor Residual Spraying (IRS). These measures prevented more than 78 million malaria cases between 2000 and 2015.
Is Gene Drive Research Losing Traction?
35023Gregory C. Lanzaro and Ana M. Kormos, The American Journal of Tropical Medicine and Hygiene, 2025-08-12 16:18:27.
Significant progress has been made in developing gene drives, especially for mosquito vectors of malaria. It is widely agreed that a critical next step in advancing this technology is to evaluate it through small-scale field trials. However, obtaining permission to move forward with these trials has stalled, threatening this potentially transformative line of research. In this paper, roadblocks delaying progress are identified from the perspective of a developer group tasked with translating this technology to the field. We suggest that groups engaged in long-running discussions about risk and the formulation of a global regulatory framework are hindering progress. This is because these groups conflate large-scale deployment with small-scale trials, which have very different risk landscapes. Here we argue that confined field trials are essential for accurately assessing risk and should be conducted soon, with regulation by authorities in the country in which they will be conducted.
Sequence mismatch between gene-drive and target-site flanking regions significantly impairs homing efficiency in Culex quinquefasciatus
35007Tim Harvey-Samuel, Rajdeep Kaur, Philip T Leftwich, et al., bioRxiv, 2025-08-04 11:03:26.
CRISPR/Cas9-based homing gene-drives (homing-drives) hold enormous potential as control tools for mosquito disease-vectors. These genomically-encoded technologies spread themselves through target populations by creating double-stranded DNA breaks on homologous chromosomes, into which the homing-drives are copied (homed). Homing is dependent on sequence homology between the genomic regions flanking the transgene insertion and the break site. Homing efficiency (i.e. copying rate) substantially impacts the power of these systems: less efficient homing-drives spread slower, have fewer applications and are more resistance-prone. Understanding what influences homing-drive efficiency is therefore vital to the successful use of these technologies. Here we report a novel mechanism by which a homing-drives efficiency can be significantly impaired by natural sequence variation within a population into which it is spreading. Using a kmo-targeting split homing-drive in the West Nile virus mosquito Culex quinquefasciatus, we found that target-site heterology (sequence mismatch between the genomic regions flanking the target cut-site and the homing-drive transgene) of less than 10% reduced homing efficiency by up to 54%. While substantial research effort has been dedicated to increasing homing-drive efficiency through optimisation of within-construct components, our results highlight that the real-world efficacy of these systems may in part depend on variation beyond these controllable factors.
Controversial ‘gene-drive’ strategy could make mosquitoes hostile to malaria parasites
34977Mitch Leslie, Science, 2025-07-24 09:37:48.
To fight malaria and the mosquitoes that spread it, people have drained swamps, showered their homes with insecticides, slathered themselves in noxious repellents, hidden under netting at night, and invented the gin and tonic—as a palatable way to take the bitter antimalarial quinine. Now, researchers report in Nature that they have borrowed a weapon from the mosquitoes themselves. The team genetically engineered mosquitoes to be resistant to parasites that cause malaria by inserting a version of a gene naturally found in some of the insects. They also enlisted a genetic trick known as gene drive to speed the gene variant's spread through mosquito populations in the lab. The strategy is not ready for field testing, researchers caution. But the experiments "are elegantly designed and sound, really showing great proof of principle for driving natural variants of mosquito genes into a population," says functional geneticist Tony Nolan of the Liverpool School of Tropical Medicine, who wasn't connected to the study.
A genetic tweak could prevent mosquitoes from transmitting malaria
34987Jonathan Lambert, NPR, 2025-07-23 10:40:28.
Each year, 263 million people get malaria. But from the parasite's perspective, infecting humans is harder than you might think, and requires completing an epic journey within the tiny body of a mosquito. First, the mosquito must suck the blood of an individual infected with malaria — bringing the Plasmodium parasite into the insect's gut. Then the parasite must travel to the critter's salivary glands, where it's poised to be injected into the mosquito's next victim via a bite. Now a team of researchers have found a way to interrupt this crucial journey. By using gene editing to make a tiny tweak to the mosquito's genome — one that changes just a single amino acid — parasites were largely prevented from reaching their final destination. The change effectively rendered laboratory mosquitoes highly resistant to spreading malaria, researchers report Wednesday in Nature. "The idea that you could change just one amino acid and not have the parasite transmitted is a pretty big deal," says Fred Gould, an entomologist at North Carolina State University who wasn't involved in the study. "It's really exciting." That tiny tweak could be spread through a whole mosquito population using a gene drive, a genetic technology that breaks the normal 50-50 rules of inheritance. Gene drives are sequences of DNA that can be inserted into the genome of an individual and cause a specific mutation or gene to be passed on to virtually all offspring, instead of just 50%.
Experimental Test of Evolutionary Safety of a CRISPR-Cas9 Gene-Drive Element
34958Michael S Overton, Sean E Guy, Xingsen Chen, et al., bioRxiv, 2025-07-08 13:24:10.
CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, with applications from disease eradication to species conservation. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to unintended loss-of-heterozygosity (LOH) events. These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To measure how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeast Saccharomyces cerevisiae. We found no detectable effects on the genome-wide rates of mutations or LOH events. Our power calculations suggest that CCGD or Cas9 affect these rates by less than 30%, which is much less than natural variation for these traits in yeast. A more detailed examination shows that CCGD or Cas9 may alter the lengths and genomic distributions of LOH events, but the statistical support for these effects is weak. Thus, our results demonstrate that CCGDs impose at most a weak additional mutational burden in the yeast model. Although mutagenic effects of gene drives need to be further evaluated in other systems, our results add credence to the proposition that the evolutionary risks posed by well designed gene drives are likely acceptable.
Create legal path for gene drive mosquitoes, experts say
34919Samwel Doe Ouma, The Star, 2025-06-23 10:42:22.
As Africa continues to shoulder the global burden of malaria, scientists and policy experts say gene drive technology could offer a groundbreaking solution. But without clear regulatory frameworks and strong community engagement, its deployment could be delayed, risking further loss of life and economic productivity. During the Evidence for Development (EVI4DEV) Conference in Nairobi, hosted by the African Union Development Agency (AUDA-NEPAD), the Science for Africa Foundation (SFA), and the African Institute for Development Policy (AFIDEP), experts called for urgent policy harmonisation and public dialogue to enable the safe rollout of gene drive technology. “Malaria is an African problem, we need to find our own tools to address malaria problems,” said Dr Barbara Glover from AUDA-NEPAD, South Africa. “Africa should be able to innovate new technologies and solutions for African problems.” Gene drive technology targets malaria-transmitting mosquitoes by altering their genetic makeup, specifically the Anopheles gambiae species, to pass on traits such as infertility, reducing mosquito populations over time. The approach, being developed under the Target Malaria consortium, has shown promise in laboratory settings but has not yet been tested in the field. “Gene drives systems promote the biased inheritance of specific genes from one generation to the next,” explained Dr Wiltshire Johnson of AUDA-NEPAD. “Gene drive is deployed when a causal pathway initiated by release of a gene drive system in target mosquito vector species, leading to its transmission to subsequent generations, its increase in frequency and spread in target mosquito populations, its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity of plasmodium and reduced vectorial capacity for parasites in target mosquito populations resulting in decreased malaria incidence and prevalence.” Johnson emphasised the urgency of adopting innovative tools amid increasing resistance to existing malaria interventions such as insecticides and drug treatments. “Malaria still kills 600,000 people, causes reduction of 25 percent GDP in Africa countries,” he said. “Even with existing traditional Malaria control tools starting to fail or are showing signs of failure... the deployment and use of gene drive technology will help in solving the malaria problem.”
Gene Drive Mosquitoes: Can We End Malaria?
34930The Curious Scholarette, YouTube, 2025-06-19 14:56:01.
What if we could genetically modify mosquitoes to stop malaria in its tracks? In this episode of The Curious Scholarette, we explore the groundbreaking world of gene-drive technology — a powerful tool that could eliminate malaria-carrying mosquitoes by altering their DNA. But with great power comes great ethical debate. 🔬 In this video, we break down: What gene drives are and how they work How scientists are using CRISPR to disrupt mosquito reproduction or malaria transmission Evidence from field trials and lab experiments The potential risks: ecological disruption, irreversible changes, and bioethical concerns Perspectives from global health experts, bioethicists, and community leaders 📍 Why it matters: Malaria kills over 600,000 people each year, mostly in sub-Saharan Africa. Could gene-drive mosquitoes be the silver bullet? Or are we playing with fire? 🧪 Sources Cited: WHO Malaria Report
Status of gene drive research in Africa; Ifakara Health Institute
34941African Genetic Biocontrol Consortium, YouTube, 2025-06-16 08:56:50.
The African Genetic Biocontrol Consortium is an agreement established by not-for-profit member organizations based in Africa with a vision to build an informed local leadership to support the requirements for development, decision-making and on the utility of genetic biocontrol technologies for animal, public health, and conservation in Africa. To fulfil this vision the Consortium has established a Forum for Institutional Committees in Africa (IBC - Africa Forum) to provide a platform for interaction among African experts and institutions to enhance opportunities for technical capacity strengthening, knowledge exchange and deliberation about the challenges and opportunities of genetic biocontrol technologies for the public good, which will amplify African influence on their development and provide critical input for decision-making by product developers, policy makers, and other stakeholders. An Institutional Biosafety Committee (IBC) is a committee created in an Institution in accordance with the Biosafety law or regulation in a Country. The IBC reviews, approves and oversees research involving the use of genetically modified organisms (GMOs), recombinant or synthetic DNA/RNA and other biohazards. The IBC assists the Principal Investigator, supervisors, funders, and the Biosafety Regulators with obtaining proper authorization for their studies. The Committee also approves procedures for procurement, use, storage, transportation, and disposal of bio-hazardous material.
Strengthening gene drive research in Africa through engagement, regulation, and regional cooperation
34909Dickson W. Lwetoijera, Outreach Network for Gene Drive Research, 2025-06-15 18:59:18.
On the sidelines of this year’s World Health Assembly, I had the opportunity to speak on a panel exploring the role of genomics in public health. The event, supported by the Science Summit, brought together researchers, regulators, and policymakers to examine how genomic tools can support stronger, more equitable health systems. I spoke alongside Prof. Georges Christophides of Imperial College London and Dr. Brian B. Tarimo of the Ifakara Health Institute (IHI). Together, we reflected on how gene drive technologies could strengthen the fight against malaria in Tanzania and the broader East African region, exploring progress made in gene drive research, and reflecting on what it will take to move forward. Prof. Christophides opened with a stark reminder of challenges faced in the fight against malaria: in 2023, Tanzania recorded over 8,000,000 cases and just under 25,000 malaria deaths, with 95% of the population at risk. With challenges such as insecticide resistance weakening the impact of current tools like treated nets and indoor residual spraying, the need for new interventions is necessary and unavoidable. Gene drive technologies offer one such possibility, but only if the right systems are in place to support their development and implementation. Prof. Christophides stressed the importance of strengthening frameworks that enable progress while maintaining safety and transparency. He also highlighted the need for long-term institutional partnerships, where African agencies are not just consulted, but lead the way. Dr. Tarimo focused on the importance of community engagement, a key aspect of the research. At Transmission Zero, we are working with district-level teams in areas that may host future field trials of gene drive technologies to ensure that communities are informed, involved, and heard. Engaging with local communities means recognizing that their values and concerns must shape the direction of our work from the outset. Without that trust, no technology, no matter how promising, can succeed.
Unlocking Gene Drive in Agriculture
34897Sarah Lee, Number Analytics, 2025-06-06 08:31:38.
Gene drive is a revolutionary genetic engineering technique that has the potential to transform the field of agricultural biotechnology. In this section, we will explore the definition, mechanism, and history of gene drive technology, as well as its potential applications in agriculture. Gene drive is a naturally occurring phenomenon where a particular gene or set of genes is inherited at a higher rate than expected under normal Mendelian inheritance. This is achieved through the use of CRISPR-Cas9 genome editing technology, which enables scientists to selectively modify genes and drive them through a population at an exponential rate. The mechanism of gene drive involves the following steps: Target gene identification: Scientists identify a target gene that they want to drive through a population. CRISPR-Cas9 editing: The CRISPR-Cas9 system is used to edit the target gene and introduce a gene drive element. Gene drive inheritance: The gene drive element is inherited by offspring at a higher rate than expected, leading to the spread of the modified gene through the population.
The Future of Gene Drive in Farming
34895Sarah Lee, Number Analytics, 2025-06-06 08:25:42.
The advent of gene drive technology has opened up new avenues for transforming farming practices, improving crop yields, and promoting sustainability. Gene drive is a genetic engineering technique that allows for the rapid spread of a particular gene or trait through a population, potentially revolutionizing the way we approach crop improvement and pest management. In this article, we will explore the latest advancements in gene drive technology and its potential to shape the future of farming. Gene drive has the potential to significantly improve crop yields and nutritional content by introducing desirable traits such as pest resistance, drought tolerance, and enhanced nutritional profiles. The development of pest-resistant crops, for instance, could reduce the need for pesticides, minimizing the environmental impact of farming practices. Gene drive can be used to introduce genes that confer resistance to pests and diseases, reducing crop losses and improving yields. For example, scientists have used gene drive to develop mosquitoes that are resistant to malaria. Similarly, gene drive can be used to enhance the nutritional content of crops, such as by introducing genes that increase the production of essential micronutrients like vitamin A.
We finally may be able to rid the world of mosquitoes. But should we?
34901Dino Grandoni, Wall Street Journal, 2025-06-03 08:39:56.
They buzz, they bite, and they cause some of the deadliest diseases known to humanity. Mosquitoes are perhaps the planet’s most universally reviled animals. If we could zap them off the face of the Earth, should we? The question is no longer hypothetical. In recent years, scientists have devised powerful genetic tools that may be able to eradicate mosquitoes and other pests once and for all. Now, some doctors and scientists say it is time to take the extraordinary step of unleashing gene editing to suppress mosquitoes and avoid human suffering from malaria, dengue, West Nile virus and other serious diseases. “There are so many lives at stake with malaria that we want to make sure that this technology could be used in the near future,” said Alekos Simoni, a molecular biologist with Target Malaria, a project aiming to target vector mosquitoes in sub-Saharan Africa. Yet the development of this technology also raises a profound ethical question: When, if ever, is it okay to intentionally drive a species out of existence?
Applying the Protective Precautionary Principle to the Ethical Use of Gene Drive Technology for Anopheles gambiae Suppression in Malaria Control
34879Nucharee Wongsamut, Journal of Applied Animal Ethics Research, 2025-06-02 18:16:36.
Malaria contributes to poverty and illness, which further hinder productivity and income generation. Therefore, combating malaria is crucial for breaking the vicious cycle of poverty. Genome editing technologies, such as gene drives designed to suppress Anopheles gambiae mosquito populations, the vector for malaria, have emerged as potential tools in this fight. However, a significant ethical question arises: under what conditions is the use of gene drive technology to suppress Anopheles gambiae mosquito populations justified? This article argues that the Protective Precautionary Principle can serve as a suitable framework for morally assessing such cases. Within this framework, the use of gene drive technology for Anopheles gambiae population suppression would be permissible for laboratory research only. This limited scope minimizes the risk of unforeseen negative consequences, particularly for disadvantaged populations who may have fewer resources to protect themselves from such effects.
The challenge of measuring mosquito flight performance: going beyond sterile insect technique and into transgenic and gene drive-based approaches
35311Paola Najera, Christian E. Ogaugwu, Tyler F. Chan, et al., Open Biology, 15. 2025-06-01 10:32:43.
Invasive insects inflict global costs of more than 70 billion USD annually by destroying crops and spreading disease-causing pathogens. Sterile insect technique (SIT), an insect population control method, involves the irradiation or chemical sterilization of insects to produce sterile males that are mass-released. SIT has proven effective in reducing populations of the Mediterranean fruit fly, Mexican fruit fly and screwworm fly. In the past decade, efforts to improve SIT with transgenic approaches have increased, including the development of potentially highly invasive gene drive transgenes. Determining flight capability is vital to the success of any insect control programme, and various flight assays can be used to analyse insect dispersal, flight behaviour and the mechanics behind flight. However, traditional flight assays such as mark–release–recapture become more challenging with transgenic or gene drive arthropods due to ecological concerns, while assays such as wind tunnels or flight mills/arenas may not capture the full range of flight abilities. This review seeks to cover current flight assays and their limitations as well as the requirements for flight assays to establish comparative flight ability for genetically modified insects to better prioritize strains prior to any potential field-based releases.
Commentary on Gene drive: Communication, hype, and the publics
34870Third World Network, GMWatch, 2025-05-26 21:35:34.
An article in the Journal of Medical Entomology critically reflects on the hype surrounding gene drive technologies, a novel self-spreading form of genetic modification that is designed to engineer entire populations of wild species. The author, a specialist in vector-borne diseases at the University of Montpellier, France, concludes that current communication around gene drives “often borders on propaganda rather than fostering a balanced, 2-way dialogue”. As such, “Research institutions must also exercise caution when promoting scientific advancements in press releases and media, ensuring that accurate, reliable information reaches the public.” The rhetoric surrounding gene drive technologies is often couched in pessimistic language regarding ‘conventional’ tools. The narrow biomedical focus of such discussions also fails to consider systemic forces of vector borne disease, and “often falls short in critically examining health policies or calling for socioeconomic changes”. The current situation however, provides instructive examples of advances in malaria control, including several countries being declared malaria-free, or reporting zero deaths in recent years. Achievements have been gained with multipronged approaches including in vector control, case surveillance, diagnostics, as well as socioeconomic improvement and implementation of poverty alleviation.
The state of regulatory and governance frameworks for gene drives outside of Africa
34865African Genetic Biocontrol Consortium, YouTube, 2025-05-26 21:12:33.
Regional and global perspectives on gene drive regulation. Discussion on the state of regulatory and governance frameworks for gene drives outside of Africa, covering regional priorities and challenges.
Maximising Eradication Potential of Rat Gene Drives Using a Two-Target Homing Rescue Strategy: Spatial Modelling of Empirical Data
34817Birand, A., Gierus, L., Prowse, T., Cassey, P., Thomas, P.Q., Molecular Ecology, 2025-05-04 16:12:38.
Gene drives are genetic elements with positively biased transmission and may be useful tools to suppress mammalian pests that threaten biodiversity worldwide. While gene drives are progressing in mice, less is known about their potential for invasive rat control. A recent report has provided the first data on germline gene conversion in rats, demonstrating that modest homing rates (up to 67%) can be achieved in females. Here, we apply these empirically derived values to investigate the potential of various gene drive strategies to suppress an island population of 200,000 rats, using our stochastic, spatially explicit, individual-based modelling framework. Standard homing drives embedded in haplosufficient fertility or viability genes failed to eradicate, but achieved permanent population suppression. In contrast, a two-target design with a homing rescue (HR) drive embedded in a haplolethal gene that also targets an independent fertility or viability gene demonstrated considerable suppression potential. Remarkably, an HR drive targeting a haplosufficient female fertility gene showed robust eradication even at the relatively low homing rates previously demonstrated in rats. Interestingly, homing rate had a relatively low influence on eradication probability while cutting efficiency at the haplolethal gene was critical. Further, as long as the latter was similar to the cutting and subsequent knockout of the unlinked female fertility gene, then eradication could be achieved across a range of homing rates. Together, these results suggest that modest homing rates, such as have been demonstrated in rats and other species, can potentially be leveraged for population suppression, offering new opportunities for gene drive development.
Gene drive could reshape the malaria fight and young people must be at the centre
34803Dr. Phillip Chigiya, African Leaders Malaria Alliance, 2025-04-25 12:04:22.
The only time I was ever admitted overnight in hospital was when I was five years old. I had malaria. I still remember the strange chill of the sheets, the IV line taped to my small hand, and my mother at my bedside, watching me breathe. That moment has never left me. Since then, I have moved from patient to practitioner. I have worked in clinics and hospitals across Africa, and malaria has never been far away. I have diagnosed it in children too young to speak, in teenagers missing school, and in pregnant women arriving in labour wards with dangerously low haemoglobin. Sometimes treatment is routine. Sometimes it is a race against time. It is easy to be swept up by bold declarations, especially on World Malaria Day. But we must be honest. The progress we once celebrated is stalling. In 2023, there were over 263 million new malaria cases and an estimated 597,000 deaths, most of them in Africa. One child dies every minute. Behind every number is a name, a family, and a future lost too soon.
Stronger population suppression by gene drive targeting doublesex from dominant female-sterile resistance alleles
34799Weizhe Chen, Ziye Wang, Jackson Champer, bioRxiv, 2025-04-23 11:00:18.
CRISPR homing drives can be used to suppress a population by targeting female fertility genes. They convert wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after DNA cleavage. However, resistance alleles produced by end-joining pose a great threat to homing drive. They prevent further recognition by Cas9, and therefore weaken suppressive power, or even stop suppression if they preserve the function of the target gene. We used multiplexed gRNAs targeting doublesex in Drosophila to avoid functional resistance and create resistance alleles that were dominant female-sterile. This occurred because the male dsx transcript was generated in females by disruption of the female-specific splicing acceptor site. We rescued dominant sterility of the drive by providing an alternate splicing site. As desired, the drive was recessive female sterile and yielded high drive inheritance among the progeny of both male and female drive heterozygotes. The dominant-sterile resistance alleles enabled stronger suppression in computational models, even in the face of modest drive efficiency and fitness costs. However, we found that male drive homozygotes were also sterile because they used the rescue splice site. Attempts to rescue males with alternate expression arrangements were not successful, though some male homozygotes had less severe intersex phenotypes. Though this negatively impacted the drive, models showed that it still had significantly improved suppressive power. Therefore, this design may have wide applicability to dsx-based suppression gene drives in a variety of organisms with intermediate homing drive performance.
Uganda grapples with malaria burden amidst promising innovations
34795Innocent Lawrence Okima, The Independent, 2025-04-23 10:42:44.
According to the report, Uganda, with a population of close to fifty million people, accounts for 5% of the world’s malaria cases and 3% of malaria-related deaths. Astonishingly, according to page 151 of the report, Uganda leads the East and Southern African countries with 23% of malaria cases and high transmission rates, beating even Mozambique, which comes in second at 19%. It’s not exactly the kind of competition anyone wants to win. Malaria’s economic toll is just as staggering. Families lose loved ones, and resources that could have contributed to building roads, schools, create jobs are diverted to fight malaria. Children – the main victims of malaria – lose access to education and young children often die (80% of malaria deaths are children under five). Pregnant women are at high risk of losing their babies and their lives because malaria in pregnancy puts them in grave danger. Uganda’s government, together with partners like WHO, has declared a fight against malaria. This includes distributing insecticide-treated mosquito nets (ITNs), spraying homes with indoor residual insecticides (IRS), and ensuring early diagnosis through rapid diagnostic tests (RDTs). Treatment relies heavily on artemisinin-based combination therapies (ACTs), which remain a mainstay in the battle against the disease. While these measures have shown results—malaria prevalence has declined slightly over the last decade—progress is hampered by challenges like insecticide resistance, inadequate healthcare in remote areas, and insufficient funding. Not to mention the eternal struggle of getting children to sleep under the mosquito net and fishermen not to use it as one of their equipment to trap silverfish locally known as “Mukene”. Amid these challenges, hope emerges in the form of a genetic technology called “gene drive”, currently under development, and championed by Target Malaria at the Uganda Virus Research Institute in Entebbe. This cutting-edge approach involves genetic modifications to the Anopheles gambiae mosquito, the main malaria carrier in Uganda.
International perspectives on the meaning of engagement in biotechnology risk assessment: the case of gene drive
34789Hartley, S., Stelmach, A., Kokotovich, A., & Smith, R. D. J., Journal of Risk Research, 2025-04-23 10:10:43.
Biotechnology remains challenging for risk assessors. The risk assessment of genetically modified organisms was the locus of considerable, acrimonious, and politicised debate and subjected to intense scrutiny. Since then, biotechnology has evolved to include new tools, such as genome editing and gene drive, and risk assessors are more sensitive to stakeholder and public views. While engagement is increasingly recognised as important in risk governance, it is underrepresented in the governance literature, remains challenging in risk assessment, and needs empirical cases to develop theory. Imagining engagement in risk assessment will require thinking about when, where, and how to engage people in risk assessment processes in both research and regulatory contexts. However, current risk assessment methods and processes make engagement of non-technical experts challenging and risk assessors may need to innovate and diverge from the norms of risk assessment. Gene drive presents a case of risk assessment that has generated a plethora of prescriptive calls and recommendations for engagement. We use this case study to explore how both technical and non-technical experts and stakeholders involved in gene drive risk assessment are imagining engagement. We conduct qualitative, interpretive research, drawing on 30 interviews with participants across five continents. We show that the people involved with engagement in risk assessment are talking about drastically different things when they talk about engagement. Placing an empirical and theoretical spotlight on engagement in risk assessment, we argue that conversations need to draw on our insights to move beyond simply recognising, justifying, and calling for engagement.
Mathematically modelling the population dynamics of CRISPR gene drive systems in the pine pest Sirex noctilio
34779Strydom, H., Ouifki, R., Chapwanya, M., bioRxiv, 2025-04-18 10:34:17.
Sirex noctilio is an invasive pest of pine that has caused significant economic damage in South Africa and many other Southern Hemisphere countries. Current management tools are not efficient in all cases and consequently there is a need for more efficient and targeted control measures. An emerging tool for pest management is the use of gene editing and associated gene drive systems. In this study, we aim to investigate the use of CRISPR-Cas gene drive systems in the management of S. noctilio in South Africa. As a first step, we developed a model for the population dynamics of S. noctilio, using historical national population monitoring data and incorporating the influence of two main biological control agents of the pest. We then modelled the influence of two different CRISPR-Cas systems on the population dynamics of S. noctilio namely, a baseline CRISPR model and Complementary Sex Determination CRISPR (CSD) model. Each model is used to simulate a male and female only introduction strategy to estimate the effectiveness of different methods of introducing the gene drive system. The model calibration was achieved by optimizing the model fit to existing data using the least squares technique. Results suggest that both CRISPR gene drive systems would be effective at controlling the population growth of S. noctilio at high levels of introduction, but overall population control would be hindered by practical limitations. Although only two CRISPR models were explored, the underlying population model serves as a framework for further studies into the population dynamics of Sirex noctilio, as well as many other CRISPR-Cas gene drive systems.
Innovative video game brings gene drive technology to life in Africa’s fight against malaria
34769African Media Agency, Business Ghana, 2025-04-17 09:53:12.
Ahead of World Malaria Day, Target Malaria, a not-for-profit research consortium pioneering genetic technologies for malaria control, hosted a live demonstration this month of its educational video game, Target Malaria: The Game. This interactive tool is reshaping how science is communicated by making complex genetic technologies accessible, engaging, and fun. Originally launched at the end of 2024, the educational game places players in the role of a lab technician working on genetically modified mosquitoes — a potential tool for vector control being explored to eliminate malaria in Africa. It introduces players of all ages and backgrounds to the real-world tools and processes of molecular biology through two modules: “Microinjection” and “Transgenic Screening.” In “Microinjection”, players simulate injecting a DNA solution into mosquito embryos, and in “Transgenic Screening”, players sort fluorescent, genetically modified mosquito larvae. “This isn’t just a game — it’s a capacity-building tool,” says Louise Marston, Senior Research Technician for Target Malaria at the Crisanti Lab, in Imperial College London and who conceived the idea for the game. “We’re demonstrating how a digital experience can bring scientific discovery to life, even in low-connectivity environments.”
A predatory gene drive for targeted control of self-transmissible plasmids
34734Ryan Tsoi et al., Science Advances, 11. 2025-04-03 17:09:42.
Suppressing plasmid transfer in microbial communities has profound implications due to the role of horizontal gene transfer (HGT) in spreading and maintaining diverse functional traits such as metabolic functions, virulence factors, and antibiotic resistance. However, existing tools for inhibiting HGT are limited in their modes of delivery, efficacy, and scalability. Here, we present a versatile denial-of-spread (DoS) strategy to target and eliminate specific conjugative plasmids. Our strategy exploits retrotransfer, whereby an engineered DoS plasmid is introduced into host cells containing a target plasmid. Acting as a predatory gene drive, DoS propagates itself at the expense of the target plasmid, through competition or active elimination. Once the target plasmid is eradicated, DoS is removed via induced plasmid suicide, resulting in a community containing neither plasmid. The strategy is tunable and scalable for various conjugative plasmids, different mechanisms of plasmid inheritance interruption, and diverse environmental contexts. DoS represents a new tool for precise control of gene persistence in microbial communities.
Genetically modified mosquitoes released in the US: How they can prevent disease outbreaks
34732TOI Lifestyle Desk, Times of India, 2025-04-02 16:42:21.
The menace of mosquito-borne illnesses is growing in the US and the contributing factors range from climate change to their expanding habitats. The solution could lie in genetically modified mosquitoes that hold the capability to effectively control mosquito populations. Recently, genetically modified mosquitoes were released in Florida, US, following the successful trials in Brazil, the Cayman Islands, Panama, and Malaysia, where populations of aedes aegypti dropped by at least 90%. A significant step forward in preventing the deadly mosquito-borne illnesses, the bioengineered male aedes aegypti mosquitoes were introduced into the environment. While these deadly species make up for 4% of the total local mosquito population, they are enough to wreak havoc. It is to be noted that female aedes aegypti mosquitoes are the primary vectors that can transmit dengue, Zika, yellow fever, and chikungunya viruses to humans.
AUDA-NEPAD launches the 2nd edition APET report on gene drives for malaria control and elimination
34657Charles Mugoya, Target Malaria, 2025-03-25 09:09:33.
With support from the African Union Development Agency (AUDA-NEPAD), the African Union published its 1st APET report in 2018 which noted that that, while the existing mosquito control interventions have significantly reduced the burden of malaria across Africa, complementary new interventions were very much needed to drive the residual burden towards zero and eventually achieve malaria elimination on the continent. African countries were urged to invest in the development and regulation of gene drive technology, whose greatest and most urgent application will be in malaria control and elimination. To this end, African Union (AU) held a Summit in Addis Ababa from 10 -15 February 2025 in which, AUDA-NEPAD took the opportunity to organize a side event to launch the 2nd APET report. The report provides very useful insights on genetically based vector control tools in general and gene drive in particular. The 2nd APET edition report comprises 9 sections that convey messages to update a diverse community of stakeholders on progress and current state of research and development efforts with recommendations for gene drive technology advancement.
Gene drives. Technologies for spreading genetic modifications in populations. TAB-Fokus
34652König, H., Kolleck, A., Sauter, A., TAB-Fokus, 48. 2025-03-21 07:04:16.
Gene drives have the potential to help solve major challenges, including the fight against invasive species or vector-borne diseases such as malaria. These hopes are offset by technical and scientific challenges as well as environmental risks. The policy brief TAB-Fokus no. 48 on the opportunities and risks of a technology for spreading desirable traits in populations summarises the most important results of the TA project for the German Bundestag on four pages (and is also available as a web version - see relation in KITopen). Detailed results can be found in the final report - see relation in KITopen).
Ghana committed to exploring gene drive to combat malaria – Minister
34638Ghana News Agency, 2025-03-20 14:31:41.
Ghana has expressed interest in exploring gene drive technology as a new approach to combatting malaria. The country is open to adopting technology that is cost-effective, efficient, harmless and has the potential to significantly reduce malaria transmission, especially in areas where traditional control methods have failed. Dr. Ibrahim Murtala Muhammed, the Minister of Environment, Science, and Technology gave the assurance in an interview with journalists after opening the Second Global Genetic Biocontrol Congress in Accra. Scientists, researchers, and stakeholders from 25 institutions drawn from 15 countries are participating in the conference on the theme: “Harnessing genetic biocontrol potential solutions in changing climate.” Describing Malaria as a “serious threat,” Dr. Muhammed said the burden of malaria on Africa’s economy was high as the continent spent millions of dollars on malaria control. He said Ghana would adopt emerging technologies to help support disease prevention including those that affect crops “as long as it does not affect our survival as human beings.” People who are against GMO have several cultural issues and social issues. But the question is, is it the way to go now?
Inside the lab breeding malaria resistant GM mosquitoes
34618Reuters, YouTube, 2025-03-18 12:02:59.
An international team of scientists are developing genetically modified mosquitoes that can slowly convert the entire wild population of mosquitoes resistant to transmitting malaria, the world’s most deadly disease.
What Is Gene Drive? – Biology For Everyone
34607Biology for Everyone, YouTube, 2025-03-18 11:07:30.
What Is Gene Drive? In this informative video, we will introduce you to the intriguing concept of gene drive, a revolutionary technology that enables the rapid transmission of specific traits within a species. We will break down the mechanics of how gene drive works, including the role of genetic engineering tools like CRISPR-Cas9. You will learn about the process of inserting a gene drive into an organism's DNA and how it ensures that the desired genes are passed on to nearly all offspring. We'll also discuss the various applications of gene drives, including their potential to combat insect-borne diseases such as malaria, dengue, and Zika, as well as their use in managing invasive species and addressing pesticide resistance. Additionally, we will explore the different types of gene drives, such as homing-based gene drives and sex distorter drives, and how these methods can impact populations. While the potential of gene drives is exciting, we will also touch on the associated risks and the importance of careful management to prevent unintended consequences. Join us for this engaging discussion, and subscribe to our channel for more enlightening content on biology and genetic technologies.
Monitoring Gene Drives: A Living Literature Review on Gene Drive Research
34604International Centre for Genetic Engineering and Biotechnology, Monitoring Gene Drives, 2025-03-18 10:58:53.
Literature reviews have always been essential for summarizing the current state of a research field. However, in areas that evolve rapidly—like gene drive technology—traditional reviews can become outdated quickly. While peer-reviewed research is invaluable for pinpointing knowledge gaps and shaping best practices, it can be challenging for practitioners, and even researchers, to keep up with the latest insights due to time constraints, paywalls, and the complexity of different research methods. We believe a more agile, inclusive, and accessible approach is needed to keep scientific understanding timely and relevant. Living literature reviews can help address this need by providing ongoing, curated updates of the latest research. Unlike classical genetically modified organisms, the first gene drive organisms likely to be released will be wild species (e.g., Anopheles mosquitoes, screwworm flies, or mice) that can cross borders. This raises multifaceted regulatory, ecological, and ethical questions, sparking complex international discussions. To navigate these debates, stakeholders require current, evidence-based information about gene drive research. Monitoring Gene Drives serves as an accessible, continuously updated resource consolidating the most recent findings on gene drive research. This initiative aims to support informed policymaking, decision-making, and public dialogue by ensuring that stakeholders have accurate and up-to-date insights in a field where new studies are constantly reshaping the landscape.
Gene drive modified mosquitoes offer new tool for malaria elimination efforts
34615Conrad Duncan, Imperial, 2025-03-13 11:59:36.
Transmission Zero, a research team from Imperial College London in partnership with the Ifakara Health Institute and the National Institute of Medical Research in Tanzania, has developed genetic technology which renders a mosquito unable to transmit the malaria parasite and has a gene drive that ensures that future generations are also resistant to the parasite. The technology could significantly reduce the malaria burden in high-risk countries, saving hundreds of thousands of lives each year, especially among children – who are disproportionately at risk from the disease. The work of Transmission Zero has been highlighted in a new Global Development Hub STEM for Development Impact Memo authored by Professor George K. Christophides, Professor of Infectious Disease and Immunity at Imperial, Dr Nikolai Windbichler, Reader in Genetics at Imperial, and Dr Dickson Wilson Lwetoijera, Principal Research Scientist at Ifakara Health Institute in Tanzania. Professor Christophides from Imperial’s Department of Life Sciences said: “The solutions we currently have for malaria are not enough – we need something new. “Our technology is equitable, it offers hope in the fight against malaria and doesn’t present economic or social barriers to malaria intervention access.”
2nd Edition Report: Gene Drives for Malaria Control and Elimination in Africa
34579African Union High-Level Panel on Emerging Technologies, APET Secretariat, 2025-03-12 16:43:52.
Malaria continues to impose a significant economic and public health burden on Africa. In 2021, the continent accounted for 95% of the global 247 million new malaria cases and 96% of the 619,000 malaria-related deaths. Notably, over three-quarters (77%) of these deaths occurred among children under the age of five. At present, ten countries—Burkina Faso, Cameroon, the Democratic Republic of the Congo, Ghana, Mali, Mozambique, Niger, Nigeria, Uganda, and the United Republic of Tanzania—have been classified as High Burden, High Impact (HBHI) nations, collectively contributing to 68% of all malaria cases and 70% of malaria-related fatalities globally. Furthermore, approximately 1,031,000,000 individuals across Africa are estimated to be at risk of contracting malaria. Extensive studies have consistently demonstrated a strong correlation between economic development rates and the burden of malaria, underscoring malaria’s role as a critical impediment to economic progress. The direct economic costs of malaria are substantial, placing immense strain on the limited resources of the affected African nations. Countries severely burdened by malaria exhibit Gross Domestic Products (GDPs) that are up to five times lower than those of malaria-free nations. The annual economic growth loss in endemic countries is estimated at 1.3%, equating to as much as US$12 billion in lost productivity. Moreover, malaria contributes to between 5-8% of school absenteeism among African children and causes an additional 2.4 to 6.5 days of absenteeism per student. The costs associated with malaria prevention and treatment further highlight the economic challenge. The annual cost of protecting one individual against malaria ranges from US$1.18 to US$5.97 through vector control measures. Diagnosis costs have a median of US$6, while treatment costs for each case vary depending on severity, ranging from US$9 to US$89.93. As such, malaria remains the foremost public health priority in Africa, with the costs of treatment and disease prevention far exceeding the financial capacities of most African governments. A further pressing concern is the recent introduction and establishment of Anopheles stephensi, a species of mosquito that poses a significant threat to the Horn of Africa and beyond. This invasive species, which tends to bite outdoors, could exacerbate the existing malaria burden and undermine the gains made in malaria control over the past two decades. The global response to malaria control heavily relies on donor funding, which is currently only sufficient to meet half of the required global funding targets. This reliance on external financing is unsustainable and highly vulnerable to shifts in political priorities in donor countries. Approximately a quarter of the global malaria funding is directed to Africa for the provision of insecticide-treated nets, rapid diagnostic tests, and medicines, while national funding should cover the operating costs of the broader health sector. Existing malaria control measures, including the use of Long-Lasting Insecticidal Nets (LLINs), Indoor Residual Spraying (IRS), and Larval Source Management (LSM), have demonstrated limited effectiveness, especially against the newly introduced invasive mosquito species. This underscores the necessity for the development and adoption of innovative mosquito control approaches, such as Attractive Targeted Sugar Bait (ATSB), Endocticides, Improved Housing, Sterile Insect Technique (SIT), and Paratransgenesis. Research into these methods is ongoing, and their potential for improving malaria control strategies is considerable. To supplement existing malaria control efforts, innovative technologies like Gene Drive present promising long-term solutions to protect the most vulnerable populations and address the malaria burden in Africa. The African Union (AU) has recognised the potential of Gene Drive technology and has endorsed its development, with support from the African Union Development Agency (AUDA-NEPAD). This initiative aims to foster conducive environments for research, develop regulatory frameworks, and engage stakeholders across African Union Member States, ensuring a collaborative approach to the ongoing fight against malaria.
CRISPR/Cas9 Genome Editing in the Diamondback Moth: Current Progress, Challenges, and Prospects
34556Asad, M., Chang, Y., Liao, J., & Yang, G., International Journal of Molecular Sciences, 26:1515. 2025-03-04 11:34:07.
The development of site-specific genome-editing tools like CRISPR (clustered regularly interspaced short palindromic repeat) and its associated protein, Cas9, is revolutionizing genetic engineering with its highly efficient mechanism, offering the potential for effective pest management. Recently, CRISPR/Cas9 gene-editing has been extensively utilized in the management of the diamondback moth, Plutella xylostella (L.), a highly destructive pest of vegetable crops, for different purposes, such as gene function analysis and genetic control. However, the progress related to this gene-editing tool in P. xylostella has not yet been summarized. This review highlights the progress and applications of CRISPR/Cas9 in uncovering the genes critical for development, reproduction, and insecticide resistance in P. xylostella. Moreover, the progress related to the CRISPR/Cas9 gene drive for population suppression and modifications has also been discussed. In addition to the significant progress made, challenges such as low germline editing efficiency and limited homology-directed repair remain obstacles to its widespread application. To address these limitations, we have discussed the different strategies that are anticipated to improve the efficiency of CRISPR/Cas9, paving the way to it becoming a pivotal tool in sustainable pest management. Therefore, the present review will help researchers in the future enhance the efficiency of the CRISPR/Cas9 system and use it to manage the diamondback moth.
Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae
34552Andrea L Smidler, Eryney A Marrogi, Sean Scot, et al., bioRxiv, 2025-03-04 11:03:46.
Gene drives are selfish genetic elements which promise to be powerful tools in the fight against vector-borne diseases such as malaria. We previously proposed population replacement gene drives designed to better withstand the evolution of resistance by homing through haplolethal loci. Because most mutations in the wild-type allele that would otherwise confer resistance are lethal, only successful drive homing permits the cell to survive. Here we outline the development and characterization of two ΦC31-Recombination mediated cassette exchange (RMCE) gene drive docking lines with these features in Anopheles gambiae, a first step towards construction of robust gene drives in this important malaria vector. We outline adaption of the technique HACK (Homology Assisted CRISPR knockin) to knock-in two docking site sequences into a paired haplolethal-haplosufficient (Ribosome-Proteasome) locus, and confirm that these docking lines permit insertion of drive-relevant transgenes. We report the first anopheline proteasome knockouts, and identify ribosome mutants that reveal a major hurdle that such designs must overcome to develop robust drives in the future. Although we do not achieve drive, this work provides a new tool for constructing future evolution-robust drive systems and reveals critical challenges that must be overcome for future development of gene drives designed to target haplolethal loci in anophelines and, potentially, other metazoans.
RNA-guided nucleases enable a gene drive of insertion sequences in plasmids
34547Kepler S. Mears, Fernando W. Rossine, Natalia Quinones-Olvera, et al., bioRxiv, 2025-03-04 10:40:44.
Mobile genetic elements (MGEs) and the interactions between them are a major source of evolutionary innovation. Insertion sequences, the simplest MGEs usually encoding only the necessary genes for transposition and maintenance, are widespread in bacterial genomes, and are particularly common in plasmids. Plasmids, self-replicating extrachromosomal DNA elements, often exist in multiple copies imparting a stochastic barrier to the fixation of an insertion sequence by limiting the proportion of the plasmid population harboring the IS. In this work we demonstrate that to overcome this, the IS200/605 family of insertion sequences utilizes programmable RNA guided nucleases as gene drive to spread the IS through the plasmid population. TnpB, the likely ancestor of Cas12, records the specific insertion site of the IS in its RNA guide to prevent loss of the IS during transposition. When introduced to a plasmid TnpB will be reprogrammed to target and cleave IS-plasmids, resulting in biased replication of IS+ plasmids. Furthermore, the gene drive activity is critical for the IS to invade high copy plasmid populations. Because TnpB can only be mobilized between microbes on other mobile genetic elements, this advantage to fixing in plasmids may help explain the prevalence of TnpB across the tree of life. More generally, the unique pressures arising from movement between genetic contexts with different multiplicities shapes the evolution of strategies for MGE spread.
A Gene Drive with a Disappearing Act Can Aid Pest Control
34537Shelby Bradford, PhD, The Scientist, 2025-02-21 12:02:41.
Geneticists developed a gene drive that reverts insecticide-resistant mutations in insects, using a system that gradually eliminates itself from the genome. This breakthrough offers a potential solution to combat insecticide resistance without permanently altering species, and could be adapted to mosquitoes and other pests in the future.
What are the evolutionary considerations of rodent gene drives for conservation and human health?
34662Triangle Center for Evolutionary Medicine, YouTube, 2025-02-21 09:38:19.
Biodiversity, human health, and food security can all be impacted by invasive rodents. These negative impacts are particularly seen on islands, where rodent eradications with traditional methods can sometimes fail due to evolutionary resistance. Gene drives may offer an approach to the challenge of rodent eradication on islands. My primary research focus is wild house mice (Mus musculus) and the potential use of gene drive technology. Mus are a key genetic model system and an invasive species on many islands worldwide. Evolutionarily sound approaches are needed, and we are investigating ways to tailor genetic techniques to unique island populations. Using models on gene drive mice can help us predict how laboratory/wild mice would introgress into a population. Evolutionary resistance is also possible; the mice may evade our best methods. However, gene drive technology in rodents can potentially produce significant gains for conservation and society. To this end, a broad interdisciplinary lens with many differing perspectives is required.
Integrating malaria vaccine and CRISPR/Cas9 gene drive: a comprehensive strategy for accelerated malaria eradication
34374Abraham, I.C., Aboje, J.E., Ukoaka, B.M. et al., Malaria Journal, 24. 2025-01-28 15:04:09.
Malaria remains a significant public health challenge, particularly in low- and middle-income countries, despite ongoing efforts to eradicate the disease. Recent advancements, including the rollout of malaria vaccines, such as RTS,S/AS01 and R21/Matrix-M™, offer new avenues for prevention. However, the rise of resistance to anti-malarial medications necessitates innovative strategies. This review explores the potential integration of CRISPR/Cas9 gene drive technology with malaria vaccination efforts to enhance vector control and reduce transmission. By employing gene drive mechanisms for population suppression and replacement of malaria-transmitting Anopheles mosquitoes, combined with the immunogenic properties of vaccines, a synergistic approach can be established. This paper discussed the need for integrated strategies to address the biological complexities of malaria and socio-economic factors influencing its prevalence. Challenges such as regulatory hurdles, community acceptance, ecological impacts, and sustainable funding are examined, alongside strategies for implementation within existing malaria control programmes. This integrated approach could significantly contribute to achieving the World Health Organization's targets for malaria reduction by 2030, ultimately enhancing public health outcomes and supporting broader socio-economic development.
Gene Drive Technology Offers Hope For Malaria Vector Control
34365Evrim Ağacı, The Pinnacle Gazette, 2025-01-28 13:46:11.
A team of scientists has developed an innovative gene drive targeting Anopheles stephensi mosquitoes, a key malaria vector in urban areas. Their strategy uses CRISPR technology to disrupt the doublesex (dsx) gene, crucial for female fertility, thereby reducing mosquito populations. The gene drive, called HSDdsx, showed promising results in suppressing mosquito reproduction with minimal resistance, indicating long-term effectiveness. This approach could help control malaria transmission and reduce reliance on pesticides. The research also opens doors for future advancements in pest control, with potential applications against other disease vectors, marking a significant step toward environmentally friendly solutions.
Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti
34261Yang, X., Xu, X., Chen, Y. et al., Journal of Pest Science, 2025-01-14 09:57:33.
Aedes aegypti, known for transmitting viruses such as dengue, Zika and yellow fever, poses a significant public health threat. Conventional insecticides give rise to a range of issues, including ecological contamination and insect resistance. Hence, there is a pressing demand for environmentally-friendly, safer and more efficacious strategies for mosquito control. With the rapid advancement of the CRISPR/Cas9 system in gene function exploration and pest population control, substantial progress has been achieved in utilizing CRISPR/Cas9-based gene drive systems across various mosquito species. Only a few studies on gene drive technology have been conducted in Ae. aegypti. In this study, we constructed two complete drives for Ae. aegypti with different Cas9 promoters, each targeting kmo. Our drive based on PubCas9 had limited activity, but one with ExuCas9 exhibited super-Mendelian inheritance rates of approximately 60%. We observed low but detectable somatic activity of the drive and no evidence of maternally deposited Cas9. Germline resistance allele formation rates were similar to drive conversion rates, but most wild-type alleles in the germline remained uncut. Injections into the ExuCas9 drive line had 100% knockout efficiency among surviving offspring at three separate target genes. These results support the development and application of novel genetic pest control technologies aimed at combating Ae. aegypti.
For the Sake of 600,000 Children, Science Must Be Bold
34053Laurie Zoloth, The New York Times, 2024-12-16 14:36:13.
Bold ideas in science research used to thrill us; now they seem pretty threatening. When I have written about the ethics of genetically engineered mosquitoes to combat malaria, many of my friends have expressed alarm. “What if it goes badly wrong?” they ask. What if there are unintended consequences that ripple across ecosystems? What if this is one of those technologies that cross the line from innovative to utterly world-destroying And yet, one could also ask, what if we do nothing? For that question, at least we have an answer. A report last week from the World Health Organization reveals that 597,000 people died of malaria last year, overwhelmingly children under age 5, and an estimated 263 million people were sickened. Thousands of families cradled a baby dying from a preventable fever; thousands of pregnancies ended in stillbirth or maternal death. For a time in the early 2000s, it seemed as if the world was gaining ground against malaria, but progress has stalled, cases have risen and the hopes for its near-elimination by 2030 have been scuttled. Global warming, armed conflict and lack of funding are all factors. And while new vaccines certainly will help, they are limited in their effectiveness (they reduce the risk of severe malaria by 30 percent and require four separate clinic visits). For much of the world’s poor, we still rely on the 19th-century technology of bed nets and insecticide. For the past two decades, scientists have explored whether a new technology known as a gene drive might hold the tantalizing promise of eliminating malaria by targeting the mosquitoes that carry the deadly parasite. The reason the gene drive is so potentially revolutionary — but disturbing — is that it uses genetic engineering to introduce changes in mosquitoes that do not stop with one generation, but are preferentially inherited by all future generations.
Assessing the Efficacy of Gene-Drive Technology in Reducing Malaria Transmission in Sub-Saharan Africa: Current Progress and Future Prospects
33876Bizimana Rukundo T., IAA Journal of Applied Sciences, 12(1):1-5. 2024-12-10 16:43:06.
Malaria continues to pose a significant public health challenge in Sub-Saharan Africa, necessitating innovative solutions to combat its transmission. This review examined the efficacy of gene-drive technology as a novel approach to reducing malaria transmission through genetic modifications of Anopheles mosquitoes. Utilizing a comprehensive literature review and analysis of experimental studies and pilot projects, we assessed the mechanisms of gene drives, including population suppression and replacement strategies. The findings indicated that gene-drive technology has the potential to significantly alter mosquito populations, thereby diminishing the burden of malaria. However, challenges such as ecological concerns, regulatory complexities, and public acceptance must be addressed for successful implementation. The integration of gene drives with existing malaria control measures, collaborative research efforts, and robust ethical governance is crucial for maximizing effectiveness and ensuring sustainable outcomes. Furthermore, monitoring and evaluation systems are essential for assessing the safety and efficacy of gene-drive initiatives. This review underscored the transformative potential of gene-drive technology in malaria prevention, advocating for continued dialogue among stakeholders to navigate the complexities associated with its application in Sub-Saharan Africa.
Most advanced gene drive projects
33625Gene Drive Monitor, 2024-11-12 17:33:29.
This infographic shows the species in which a gene drive has actually been built and is at least partially functional, up to 1 March 2024. Note that gene drives have been proposed in many more species, as shown our taxonomic list of targets here. Along with gene drives it includes sex ratio distorters, a similar genetic technology that also aims to suppress or eliminate populations.
Exploring The Dynamics of Gene Drive Mosquitoes Within Wild Populations Using an Agent-Based Simulation
33614S. Wickramasooriya, I. Mahmood, et al., IEEE Xplore, 2024-11-12 13:33:12.
Gene drive technology is emerging as a potentially powerful tool in combating vector-borne diseases – notably malaria. This study introduces an agent-based model (ABM) focused on the deployment of genetically engineered mosquitoes with gene drive (GEM) in Príncipe Island, Republic of São Tomé and Príncipe, an island nation in the Gulf of Guinea, West Africa. Grounded in empirical data from laboratory and field studies, our model forecasts the dynamics of mosquito populations central to devising efficacious GEM release strategies. The core objective is to evaluate the time required for GEMs to constitute 90% of the mosquito population and to elucidate their dispersal throughout the island. This research is instrumental in understanding GEM potential in controlling malaria vectors.
TWiV 1161: Baby you can drive my gene
33394MicrobeTV, YouTube, 2024-11-04 17:40:40.
TWiV reviews continuing expansion of poliovirus type 2, removal of influenza B/Yamagata from the vaccine, Nobel Prize for miRNAs, protective immune response with a adenovirus-associated virus vector expressing a computationally designed hemagglutinin, and viral gene drive during herpes simplex 1 infection in mice.
GeneConvene Global Collaborative | Considerations for the First Field Trials of Gene Drive for Malaria
33388GeneConvene Global Collaborative, YouTube, 2024-11-04 17:19:36.
A webinar organized by the GeneConvene Global Collaborative discussed the potential first field trials of gene drive technology for malaria control. This genetic modification approach aims to alter mosquito populations to reduce their ability to transmit malaria. While laboratory results are promising, no field trials have been conducted yet. Experts convened to explore key considerations for trial design, including efficacy, safety, and stakeholder perceptions. The challenges of indefinite spread associated with low-threshold gene drives complicate trial logistics, necessitating a phased testing approach recommended by the WHO. Key factors for site selection include regulatory structures, existing health data, and the need for isolated mosquito populations. The session aimed to share insights and foster discussion on the future of gene drive applications in malaria control.
Navigating biosafety regulatory frameworks for genetic engineering in Africa: a focus on genome editing and gene drive technologies
33383Tilahun Rabuma, Felix Moronta-Barrios, Wendy Craig, Frontiers in Bioengineering and Biotechnology, 12. 2024-11-04 16:05:02.
Genome editing and gene drive technologies are increasingly gaining attraction in Africa, with researchers exploring their potential applications in agriculture, health and the environment. Acknowledging that robust regulatory frameworks are crucial in facilitating the development and utilization of these technologies, informed decision-making is, however, being impeded by the fragmented information availability and readiness of regulatory authorities on the continent. This study investigates the regulatory frameworks governing genome editing and gene drive technologies in African countries, identifies common regulatory challenges and proposes actionable solutions. Primary data were collected through questionnaires and complemented by analyzing existing biosafety regulations from online databases and scientific literature. Our findings suggest that while a few African countries have recently updated their regulatory frameworks, many are still under discussion. Challenges to development and implementation include limited resources, expertise, awareness, and public resistance. The findings underscore the urgent need for further development in regulatory capacities. By shedding light on these challenges, our study could provide African regulators with valuable insights to guide the formulation of effective regulatory frameworks. Such frameworks are essential for harnessing the potential of genome editing and gene drive technologies while safeguarding human health and the environment in Africa.
Engineering Resilient Gene Drives Towards Sustainable Malaria Control: Predicting, Testing and Overcoming Target Site Resistance
33379Ioanna Morianou, Lee Phillimore, Bhavin S. Khatri,, bioRxiv, 2024-11-04 13:56:24.
CRISPR-based gene drives are selfish genetic elements with the potential to spread through entire insect populations for sustainable vector control. Gene drives designed to disrupt the reproductive capacity of females can suppress laboratory populations of the malaria mosquito. However, any suppressive intervention will inevitably exert an evolutionary pressure for resistance. Here, we present a pipeline for the accelerated discovery, engineering, and testing of both natural and drive-induced variants that could reverse gene drive spread. We applied our method to stress-test a highly effective gene drive that has evaded resistance in all laboratory-contained releases to date, known as Ag(QFS)1. We showed that previously undetected resistant alleles can arise at low frequency, and discovered novel, partially resistant alleles that can perturb drive-invasion dynamics. We then engineered next-generation gene drives that can actively remove resistant alleles by targeting several highly conserved and non-overlapping sites in the female-specific exon of the doublesex gene. Our models predict that such gene drive designs could suppress large, natural populations of the malaria mosquito in the field.
Parental-effect gene-drive elements under partial selfing, or why do Caenorhabditis genomes have hyperdivergent regions?
33170Matthew V Rockman, Genetics, 2024-10-31 08:57:53.
Self-fertile Caenorhabditis nematodes carry a surprising number of Medea elements, alleles that act in heterozygous mothers and cause death or developmental delay in offspring that don’t inherit them. At some loci, both alleles in a cross operate as independent Medeas, affecting all the homozygous progeny of a selfing heterozygote. The genomic coincidence of Medea elements and ancient, deeply coalescing haplotypes, which pepper the otherwise homogeneous genomes of these animals, raises questions about how these apparent gene-drive elements persist for long periods of time. Here I investigate how mating system affects the evolution of Medeas, and their paternal-effect counterparts, peels. Despite an intuition that antagonistic alleles should induce balancing selection by killing homozygotes, models show that, under partial selfing, antagonistic elements experience positive frequency dependence: the common allele drives the rare one extinct, even if the rare one is more penetrant. Analytical results for the threshold frequency required for one allele to invade a population show that a very weakly penetrant allele, one whose effects would escape laboratory detection, could nevertheless prevent a much more penetrant allele from invading under high rates of selfing. Ubiquitous weak antagonistic Medeas and peels could then act as localized barriers to gene flow between populations, generating genomic islands of deep coalescence. Analysis of gene expression data, however, suggest that this cannot be the whole story. A complementary explanation is that ordinary ecological balancing selection generates ancient haplotypes on which Medeas can evolve, while high homozygosity in these selfers minimizes the role of gene drive in their evolution.
Using genomics to find solutions to malaria
32714Morgan Morris, Nature Africa, 2024-10-22 17:47:10.
Joel Odero’s experiences of malaria is wide and deep. Growing up in a village in Kenya, he not only contracted the disease numerous times, but was all too familiar with the relentless daily regimen of spraying insecticides and checking malaria nets were not ripped. Decades later, as a research scientist with the Ifakara Health Institute in Tanzania, he witnessed firsthand how, for many, that daily grind is still ongoing. As part of the institute’s teams that, between 2018 and 2022, spread out across the country to capture a range of malaria-transmitting mosquitoes for studying, he would collect samples from homes where people had to spray and check their nets every day. Odero is part of a generation of scientists trying to break the stranglehold of the Anopheles mosquitoes that transmit the disease-causing parasite. Their weapon of choice is genomics. It’s a challenge taken up by organizations like Target Malaria, a not-for-profit international research consortium featuring teams in Africa, the US and Europe, and funded by, among others, the Bill & Melinda Gates Foundation and Open Philanthropy. There, researchers’ game plan is simple: reduce the population numbers of the mosquitoes, specifically those of three related species responsible for most malaria transmissions in Africa – Anopheles gambiae, Anopheles coluzzii and Anopheles arabiensis. To do so, they are looking to capitalize on a naturally occurring phenomenon, gene drive. Often described as “selfish genetic elements”, taking the form of bits of DNA code, genes are ‘driven’ when a gene that has a favorable effect becomes more prevalent in successive generations. Typically, with both humans and mosquitoes, offspring inherit two copies of any gene, one from each parent. As a result, there is a 50/50 chance of either of the two copies being passed on to later generations. Using gene drives, researchers are manipulating the bias that is introduced to that rate of inheritance so that a specific trait is nearly 100% guaranteed to be passed on. Gene-drive malaria research takes on many forms. Two of the most popular are known as ‘population replacement’ and ‘population suppression’. With population replacement, the aim is to modify the mosquitoes so that they are no longer vectors, aka transmitters, of the malaria parasite. With population suppression – which the work of Target Malaria falls under – the goal is to reduce the mosquito population. Target Malaria’s strategy is to sterilise and reduce the number of female mosquitoes. The females transmit the malaria-causing parasite known as Plasmodium falciparum to humans, and whose numbers typically determine the size of a mosquito population. The gene drive approach would be a game changer, says Target Malaria’s Abdoulaye Diabaté, head of medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences in Bobo-Dioulasso. “It’s clear that the tools that we have today are not the ones that can take us to malaria elimination,” says Diabaté. It is the failure of these ageing tools, or the fear that they might fail, that is driving the gene-based approach to malaria research in Africa and elsewhere.
The potential of gene drives in malaria vector species to control malaria in African environments
32702Hancock, P.A., North, A., Leach, A.W. et al., Nature Communications, 15. 2024-10-22 14:44:25.
Gene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of gene drives that causes vector population suppression. We simulate gene drive releases in sixteen ~ 12,000 km2 areas of west Africa that span variation in vector ecology and malaria prevalence, and estimate reductions in vector abundance, malaria prevalence and clinical cases. Average reductions in vector abundance ranged from 71.6–98.4% across areas, while impacts on malaria depended strongly on which vector species were targeted. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results show that different strategies for gene drive implementation may be required across different African settings.
Practical Application of a Relationship-Based Model to Engagement for Gene-Drive Vector Control Programs
32533Ana Kormos, Lodney Nazaré, Adionilde Aguiar dos Santos, and Gregory C. Lanzaro, The American Journal of Tropical Medicine and Hygiene, 111:341-360. 2024-10-15 12:04:35.
Engagement is an important component in the advancement of gene-drive vector control research programs as developers look to transition the technology from the laboratory to the field. As research advances and engagement surrounding this novel technology is put into practice, knowledge can be gained from practical experiences and applications in the field. A relationship-based model (RBM) provides a framework for end-user development of engagement programs and strategies. The model places end users at the center of the engagement decision-making processes rather than as recipients of predetermined strategies, methods, and definitions. Successful RBM application for healthcare delivery has previously been demonstrated, and the University of California Malaria Initiative (UCMI) has applied this model to its gene-drive program in the Democratic Republic of São Tomé and Príncipe. The model emphasizes the importance of local leadership in the planning, development, and implementation of all phases of project engagement. The primary aim of this paper is to translate the model from paper to practice and provide a transparent description, using practical examples, of the UCMI program implementation of RBM at its field site. End-user development of the UCMI engagement program provides a unique approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs. This paper may also serve as a reference and example for projects looking to establish an engagement program model that integrates end-user groups in the decision-making processes surrounding engagement.
Why are gene drive technologies being considered to help restore biodiversity on islands?
32530Outreach Network for Gene Drive Research, 2024-10-15 11:55:45.
Researchers have been studying how to harness gene drives to solve some of society’s most intractable problems for a long time. Public health and ecosystem conservation are two of the main areas where research has focused, although other uses are also possible.
A viral gene drive could offer a new approach to fighting herpes
32519Meghan Rosen, ScienceNews, 2024-10-15 08:28:16.
The words “herpes” and “spread” in the same sentence don’t typically spell good news. Unless, that is, you’re talking about a busybody new virus. That virus includes designer DNA called a gene drive that spreads from one herpes simplex virus to another. And it may be a first step toward an entirely new way of treating the infection, researchers report September 17 in Nature Communications. For now, the team has shown simply that their gene drive DNA sequence can copy/paste itself into the genomes of other herpes viruses during an infection in mice. But the idea is to one day create a gene drive virus that shuts down herpes simplex infections in people, says Keith Jerome, a virologist at the Fred Hutchinson Cancer Center in Seattle. Jerome ultimately wants to say to patients: “You don’t ever have to worry about this virus again. It’s never going to cause disease. You’re never going to infect another person. It just doesn’t matter to your life anymore.” Though some may consider herpes more annoyance than agony, “these viruses have a tremendous effect on people’s health,” Jerome says. They can cause a huge range of symptoms — some people don’t even know they’re infected while others sprout oozing sores around the genitals or mouth. Current therapies include antivirals, but they just tamp the virus down, they don’t eradicate it. One challenge is that herpes can lie dormant in people’s nerve cells for months or years and then roar awake again, spawning fresh blisters. Infection lasts a lifetime. A therapy that disables the slumbering virus could potentially cure the infection. But how to do it? Marius Walter, a Fred Hutch virologist, remembers reading an article that claimed designing gene drives in viruses was impossible. “That got me thinking,” he says.
Professor Abdoulaye Diabaté’s frank conversation with Bill Gates
32512African Media Agency, 2024-10-08 09:27:11.
On October 2, 2024, Professor Abdoulaye Diabaté, a prominent figure in malaria research and Head of Medical Entomology at Burkina Faso’s Research Institute in Health Sciences, gained international attention by appearing in the Netflix documentary series "What’s Next? The Future With Bill Gates." The episode, titled "Can We Outsmart Disease?", delves into the ongoing battle against malaria, which disproportionately affects Africa, accounting for 94% of cases and 95% of deaths globally. In his conversation with Gates, Diabaté highlights the critical link between malaria and poverty, arguing that had the disease claimed similar lives in wealthier nations, it would have prompted a more aggressive global response. He advocates for a greater role for African voices in developing innovative solutions to combat malaria, including emerging technologies like gene drive mechanisms aimed at reducing mosquito populations. Despite significant progress, recent reports indicate a worrying increase in malaria cases due to factors such as insecticide resistance and climate change. The documentary underscores the urgent need for sustained investment in malaria research and innovative approaches, a sentiment echoed by Gates, who notes the shocking disparity in funding for malaria compared to other health issues. As the series aims to raise awareness and inspire action, it poses a pressing question: Can we finally outsmart this persistent disease?
Gene Drive and Symbiont Technologies for Control of Mosquito-Borne Diseases
32504Guan-Hong Wang, Ary Hoffmann, and Jackson Champer, Annual Review of Entomology, 70. 2024-10-08 09:05:08.
Mosquito-borne diseases, such as dengue and malaria, pose a significant burden to global health. Current control strategies with insecticides are only moderately effective. Scalable solutions are needed to reduce the transmission risk of these diseases. Symbionts and genome engineering–based mosquito control strategies have been proposed to address these problems. Bacterial, fungal, and viral symbionts affect mosquito reproduction, reduce mosquito lifespan, and block pathogen transmission. Field tests of endosymbiont Wolbachia-based methods have yielded promising results, but there are hurdles to overcome due to the large-scale rearing and accurate sex sorting required for Wolbachia-based suppression approaches and the ecological impediments to Wolbachia invasion in replacement approaches. Genome engineering–based methods, in which mosquitoes are genetically altered for the modification or suppression of wild populations, offer an additional approach for control of mosquito-borne diseases. In particular, the use of gene drive alleles that bias inheritance in their favor is a potentially powerful approach. Several drives are frequency dependent, potentially giving them broadly similar population dynamics to Wolbachia. However, public acceptance and the behavior of released drives in natural mosquito populations remain challenges. We summarize the latest developments and discuss the knowledge gaps in both symbiont- and gene drive–based methods.
Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti
32128Xiaozhen Yang, Xuejiao Xu, et al., bioRxiv, 2024-10-03 09:34:32.
Aedes aegypti, known for transmitting viruses such as dengue, zika, and yellow fever, poses a significant public health threat. Conventional insecticides give rise to a range of issues, including ecological contamination and insect resistance. Hence, there is a pressing demand for environmentally friendly, safer, and more efficacious strategies for mosquito control. With the rapid advancement of the CRISPR/Cas9 system in gene function exploration and pest population control, substantial progress has been achieved in utilizing CRISPR/Cas9-based gene drive systems across various mosquito species. Only a few studies on gene drive technology have been conducted in A. aegypti. In this study, we constructed two complete drives for A. aegypti with different Cas9 promoters, each targeting kmo. Our drive based on Pub-Cas9 had limited activity, but one with exu-Cas9 exhibited super-Mendelian inheritance rates of approximately 60%. We observed low but detectable somatic activity of the drive and no evidence of maternally deposited Cas9. Germline resistance allele formation rates were similar to drive conversion rates, but most wild-type alleles in the germline remained uncut. Injections into the exu-Cas9 drive line had 100% knockout efficiency among surviving offspring at three separate target genes. These results support the development and application of novel genetic pest control technologies aimed at combating A. aegypti.
The ultra-selfish gene
31608Mathias Kirk Bonde, Works in Progress, 2024-09-18 20:59:37.
Almost every cell in our bodies contains 23 pairs of chromosomes, which are packages of the DNA and genes that provide the code for producing living things. Sperm and egg cells, however, each contain only one set of chromosomes. This set of chromosomes has been recombined from their parents’ chromosomes, meaning it contains a random mixture of segments from the parents. When a sperm and egg cell fuse, the resulting cell has a pair of each chromosome once again, resulting in 23 pairs. Because the sections of each chromosome to be passed on were selected randomly, any specific gene in a parent has only a 50 percent chance of making it to the next generation. A gene that helps organisms to have more surviving offspring will gradually become more widespread in the population. But some genes have found ways of overriding this process. For example, what if a gene makes the sperm or egg more likely to inherit the section of DNA where the gene itself is located? In that case, the selection process is no longer random, and the gene can spread across the population even if the gene carries no advantage to the animal’s fitness.
Viral gene drive spread during herpes simplex virus 1 infection in mice
31625Walter, M., Haick, A.K., Riley, R. et al., Nature Communications, 15. 2024-09-17 21:18:39.
Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we report on a viral gene drive against human herpes simplex virus 1 (HSV-1) and show that it propagates efficiently in cell culture and during HSV-1 infection in mice. We describe high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progresses from the site of inoculation to the peripheral and central nervous systems. In addition, we show evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicate that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study shows that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.
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.
Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference
31622Ruobing Feng, Jackson Champer, Molecular Ecology, 33. 2024-09-16 21:13:35.
Gene drives have great potential for suppression of pest populations and removal of exotic invasive species. CRISPR homing suppression drive is a powerful but unconfined drive, posing risks of uncontrolled spread. Thus, developing methods for confining a gene drive is of great significance. Tethered drive combines a confined system such as Toxin-Antidote Recessive Embryo drive with a strong drive such as a homing suppression drive. It can prevent the homing drive from spreading beyond the confined drive and can be constructed readily, giving it good prospects for future development. However, we have found that care must be taken when deploying tethered drive systems in some scenarios. Simulations of tethered drive in a panmictic population model reveal that successful deployment requires a proper release ratio between the two components, tailored to prevent the suppression drive from eliminating the confined system before it has the chance to spread. Spatial models where the population moves over a one-dimensional landscape display a more serious phenomenon of drive wave interference between the two tethered drive components. If the faster suppression drive wave catches up to the confined drive wave, success is still possible, but it is dependent on drive performance and ecological parameters. Two-dimensional simulations further restrict the parameter range for drive success. Thus, careful consideration must be given to drive performance and ecological conditions, as well as specific release proposals for potential application of tethered drive systems.
Understanding gene flow and its implications for gene drive research
31547Outreach Network for Gene Drive Research, 2024-09-16 09:02:52.
Gene flow is the transfer of genetic information from one population to another. Also known as gene transfer or gene migration, it plays a crucial role in the evolution and adaptation of species. Understanding the dynamics of gene flow is essential to assess the potential risks and benefits of gene drive approaches. Gene drive technology works by promoting the inheritance of a selected genetic trait within a population, leading to this trait becoming increasingly common within a specific species over time. Researchers have been studying how to harness this technology to address global challenges, including to control the transmission of vector-borne diseases and populations of invasive alien species which threaten sensitive ecosystems. Gene flow occurs naturally in the environment through two main dynamics: Vertical gene flow happens through mating, transferring genetic traits from one generation to another within a species or between closely related species. It is a natural part of evolutionary processes and plays a significant role in how traits are inherited. Horizontal gene flow involves the transfer of genes through non-sexual routes to unrelated organisms. While more common in bacteria, this type of gene flow is much less frequent in complex organisms. The potential implications of gene flow for gene drive research vary depending on specific circumstances. For example, gene drives could spread beneficial traits to malaria-carrying mosquitoes to help combat the disease. However, researchers must also consider whether the genetic modification could be passed on beyond its target population and, if so, whether it could lead to unintended impacts. Current studies indicate that gene flow between targeted and non-target species is generally unlikely due to genetic and ecological barriers. Despite this low probability, researchers continue to explore and refine gene drive technologies, notably by developing systems with built-in safeguards. These strategies aim to control how far and fast gene drives can spread by designing systems that only activate under specific conditions or within certain populations, or are self-limiting through time.
A model-informed target product profile for population modification gene drives for malaria control
31339Agastya Mondal, Héctor M. Sánchez C., John M. Marshall, medRxiv, 2024-09-03 18:44:21.
As reductions in malaria transmission in sub-Saharan Africa stagnate, gene drive-modified mosquitoes represent one of the most promising novel tools for continued disease control. In order to advance from the laboratory to the field, gene drives will be assessed against target product profiles, planning tools that list minimum criteria products should satisfy as they progress through the development pipeline. Here, we use an eco-epidemiological model to investigate parameter values for population modification gene drives that satisfy two previously-discussed target outcomes: a 50% reduction in clinical malaria incidence for a duration (window-of-protection) of at least three years, and a time-to-impact of less than one year. We consider two African settings, Burkina Faso and Kenya, where gene drive mosquitoes are currently being researched, and consider three transmission intensities at each. For the gene drive product, we explore rates of homing and resistance allele generation, fitness costs associated with gene drive and non-functional resistance alleles, and the efficacy of the effector gene(s) at reducing mosquito-to-human transmission. We find that when the window-of-protection criterion is satisfied, the time-to-impact criterion also is. Target outcomes are most influenced by the fitness cost associated with the gene drive allele and effector gene efficacy. Resistance allele parameters are also highly influential on target outcomes, and determine how long the gene drive allele persists in the population after most available wild-type alleles have been cleaved. Low rates of functional resistance allele generation are preferred, while costly non-functional resistance alleles will allow the drive allele to outcompete them. Homing rates already achieved for Anopheles gene drives do not need to be improved upon. A conundrum exists whereby the most important product parameters for predicting field efficacy are those that can only be reliably measured in the field, which presents a challenge for assessment of product readiness.
Advancements and Future Prospects of CRISPR-Cas-Based Population Replacement Strategies in Insect Pest Management
31330Zhao Y, Li L, Wei L, Wang Y, Han Z., Insects, 15. 2024-09-03 18:39:10.
Many insects are categorized as agricultural pests due to their ability to transmit diseases and damage crops, which results in significant economic losses. Scientists have proposed two main pest control strategies: population suppression, aimed at reducing the size or distribution of pest populations, and population replacement, which involves introducing genetically modified populations to replace wild pests after an initial release. Typically, population replacement strategies use gene drive systems to spread beneficial traits throughout the target population. Current promising gene drive systems include homing endonuclease genes (HEGs), Wolbachia, maternal-effect dominant embryonic arrest (Medea), and newly adapted CRISPR/Cas genome editing systems. This review provides an overview of the recent advancements in population replacement, including insights into the development, testing, and safe implementation of CRISPR-Cas-based gene drive techniques from laboratory settings to field applications. It also discusses recent developments, identifies research gaps, and offers a comprehensive analysis of genetic control strategies for insect pests.
World Mosquito Day: Gene Drives and CRISPR Technology
31205Public Health On Call, YouTube, 2024-08-27 14:16:24.
About this episode: World Mosquito Day, observed annually on August 20th, commemorates British doctor Sir Ronald Ross's discovery in 1897 that female Anopheles mosquitoes transmit malaria to humans. More than a century later, major advancements like genetically modifying mosquitoes—AKA gene drives—have the potential to reduce malaria cases and deaths dramatically, but not without hurdles. This special episode is an extended version of Malaria Minute, a podcast from the Johns Hopkins Malaria Research Institute.
Population dynamics in spatial suppression gene drive models and the effect of resistance, density dependence, and life history
31190Xinyue Zhang, Weitang Sun, Isabel K. Kim, Philipp W. Messer, Jackson Champer, bioRxiv, 2024-08-27 08:13:04.
Due to their super-Mendelian inheritance, gene drive systems have the potential to provide revolutionary solutions to critical public health and environmental problems. For suppression drives, however, spatial structure can cause “chasing” population dynamics that may postpone target population elimination or even cause the drive to fail. In chasing, wild-type individuals elude the drive and recolonize previously suppressed areas. The drive can re-enter these recolonized areas, but often is not able to catch up to wild-type and finally eliminate it. Previous methods for chasing detection are only suitable to limited parameter ranges. In this study with expanded parameter ranges, we found that the shift from chasing dynamics to static equilibrium outcomes is continuous as drive performance is reduced. To quantify this, we defined a Weighted Average Nearest Neighbor statistic to assess the clustering degree during chasing, while also characterizing chasing by the per-generation chance of population elimination and drive loss. To detect chasing dynamics in local areas and to detect the start of chasing, we implemented Density-Based Spatial Clustering of Applications with Noise. Using these techniques, we determined the effect of arena size, resistance allele formation rate in both the germline and in the early embryo from maternally deposited Cas9, life history and reproduction strategies, and density-dependent growth curve shape on chasing outcomes. We found that larger real-world areas will be much more vulnerable to chasing and that species with overlapping generations, fecundity-based density dependence, and concave density-dependent growth curves have smaller and more clustered local chasing with a greater chance of eventual population elimination. We also found that embryo resistance and germline resistance hinder drive performance in different ways. These considerations will be important for determining the necessary drive performance parameters needed for success in different species, and whether future drives could potentially be considered as release candidates.
Generating and testing the efficacy of reagents for CRISPR/Cas9 homology directed repair-based manipulations in Tribolium
31183Hannah C Markley, Kennedy J Helms, Megan Maar, Gabriel E Zentner, Michael J Wade, Andrew C Zelhof, Journal of Insect Science, 24. 2024-08-25 20:44:44.
CRISPR/Cas9 manipulations are possible in many 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 CRISPR-based (clustered regularly interspaced short palindromic repeats) genome-editing tools and methodologies are dependent upon direct experimentation. One useful technique is Cas9-dependent homologous recombination, which is a critical tool for studying gene function but also for developing pest related applications like gene drive. Here, we report our attempts to induce Cas9 homology directed repair (HDR) and subsequent gene drive in Tribolium castaneum (Herbst; Insecta: Coleoptera: Tenebrionidae). Utilizing constructs containing 1 or 2 target gRNAs in combination with Cas9 under 2 different promoters and corresponding homology arms, we found a high incidence of CRISPR/Cas9 induced mutations but no evidence of homologous recombination. Even though the generated constructs provide new resources for CRISPR/Cas9 modification of the Tribolium genome, our results suggest that additional modifications and increased sample sizes will be necessary to increase the potential and detection for HDR of the Tribolium genome.
Scientists’ novel technology to conserve mosquitoes
31459Milliam Murigi, People Daily, 2024-08-20 09:24:48.
As the world celebrates World Mosquito Day today, scientists have introduced a revolutionary technology that could conserve mosquitoes instead of killing them while eliminating some of the diseases transmitted by mosquitos. Known as gene drive technology, this innovative approach promises to eliminate malaria one of the diseases that is transmitted by mosquitos without harming the mosquito population a crucial aspect that could make this solution both effective and environmentally sustainable. “Gene drives have been successfully tested in laboratory settings to reduce mosquito fertility and spread resistance genes against the malaria parasite. There are field trials and pilot studies underway to test the effectiveness and safety of gene drives in real-world environments,” says Dr Willy Tonui. Tonui, the Chairman and Executive Director at Environmental Health Safety (EHS Consultancy Ltd) also doubles up as the Founder and Head of the Secretariat at the African Genetic Biocontrol Consortium.
Gene Drives Shown to Work in Wild Plants. They Could Wipe Out Weeds.
30936Shelly Fan, Singularity Hub, 2024-07-24 15:57:21.
Henry Grabar has had enough battling knotweed. All he wanted was to build a small garden in Brooklyn—a bit of peace amid the cacophony of city life. But a plant with beet-red leaves soon took over his nascent garden. The fastest growing plant he’d ever seen, it could sprout up to 10 feet high and grow thick as a cornfield. Even with herbicide, it was nearly impossible to kill. Invasive plant species and weeds don’t just ruin backyard gardens. Weeds decrease crop yields at an average annual cost of $33 billion, and control measures can rack up $6 billion more. Herbicides are a defense, but they have their own baggage. Weeds rapidly build resistance against the chemicals, and the resulting produce can be a hard sell for many consumers. Weeds often seem to have the upper hand. Can we take it away? Two recent studies say yes. Using a technology called a synthetic gene drive, the teams spliced genetic snippets into a mustard plant popular in lab studies. Previously validated in fruit flies, mosquitoes, and mice, gene drives break the rules of inheritance, allowing “selfish” genes to rapidly spread across entire species. But making gene drives work in plants has been a headache, in part due to the way they repair their DNA. The new studies found a clever workaround, leading to roughly 99 percent propagation of a synthetic genetic payload to subsequent generations, in contrast to nature’s 50 percent. Computer models suggest the gene drives could spread throughout an entire population of the plant in roughly 10 to 30 generations. Overriding natural evolution, gene drives could add genes that make weeds more vulnerable to herbicides or reduce their pollination and numbers. Beneficial genes can also spread across crops—essentially fast-tracking the practice of cross-breeding for desirable traits.
FILMS: Gene drive mosquitoes for malaria control
30894Sarah Hartley and Tom Law, Gene Drive Governance, 2024-07-09 08:50:21.
Gene drive mosquitoes for malaria control is a short documentary film that is beautifully shot in Uganda and explores Ugandan stakeholders’ hopes for gene drive mosquitoes – a radical new tool that offers a way to eliminate or change the mosquitoes that cause malaria. Uganda is one of the first countries in the world preparing for field trials for gene drive mosquitoes and malaria is the main cause of death in Uganda, so the stakes are high. The film builds on social science research at the University of Exeter in the UK and Makerere University in Uganda and shows how complex it is to govern gene drive.
Assessing CRISPR/Cas9 potential in SDG3 attainment: malaria elimination—regulatory and community engagement landscape
30888Snuzik, A., Malaria Journal, 23. 2024-07-07 21:42:05.
Elimination of malaria has become a United Nations member states target: Target 3.3 of the sustainable development goal no. 3 (SDG3). Despite the measures taken, the attainment of this goal is jeopardized by an alarming trend of increasing malaria case incidence. Globally, there were an estimated 241 million malaria cases in 2020 in 85 malaria-endemic countries, increasing from 227 million in 2019. Malaria case incidence was 59, which means effectively no changes in the numbers occurred, compared with the baseline 2015. Jennifer Doudna—co-inventor of CRISPR/Cas9 technology—claims that CRISPR holds the potential to lessen or even eradicate problems lying in the centre of SDGs. On the same note, CRISPR/Cas9-mediated mosquito-targeting gene drives (MGD) are perceived as a potential means to turn this trend back and put momentum into the malaria elimination effort. This paper assessed two of the critical elements of the World Health Organization Genetically modified mosquitoes (WHO GMM) Critical Pathway framework: the community and stakeholders’ engagement (inability to employ widely used frameworks, segmentation of the public, ‘bystander’ status, and guidelines operationalization) and the regulatory landscape (lex generali, ‘goldilocks dilemma’, and mode of regulation) concerning mosquito-oriented gene drives (MGD) advances. Based on the assessment findings, the author believes that CRISPR/Cas-9-mediated MGD will not contribute to the attainment of SDG3 (Target 3.3), despite the undisputable technology’s potential. This research pertains to the state of knowledge, legal frameworks, and legislature, as of November 2022.
99% gene transmission possible, China’s CRISPR tool boosts food security
30872Gairika Mitra, Interesting Engineering, 2024-07-02 12:36:50.
Chinese scientists have engineered a solution by which they could bypass natural plant gene inheritance. They aim to deploy a CRISPR-based gene editing system to help the transmission of preferred genes even when they aren’t suitable for a plant. The scientists devised a system that would use both a toxin and an antidote which would directly affect the male plant germline. Through this process, the researchers could overcome the natural Mendelian transmission rate. This can help increase the gene transmission rates up to 99% over two generations.
No Such Thing as Containment? Gene Drives for Conservation and the (Im)possibility of an Island
30864Boersma, K., Bovenkerk, B. and Ludwig, D., Philosophy and Technology, 37:75. 2024-07-02 12:23:47.
This article explores the use of islands as tools of geographical and intellectual containment - or what we call “islanding” - in the scientific and policy literature about gene drive technologies in conservation. In the first part of the article, we explore the narrative of contained gene drive use on islands and discuss how it juggles notions of localness and localization of gene drives and their (test) releases. We question the possibility and narrative of containing the spread of gene drives technologically or geographically, and argue that the gene drives for conservation literature strategically combines contradictory and reductive understandings of islands and containment. The second part of the article is devoted to reflection on nonlocal concerns about gene drives and the possibility of local gene drive decisions. We argue that attempts to legitimize local gene drives through local decision-making evade normative concerns about their nonlocalizability and risk instrumentalizing local communities for nonlocal agendas. Our overarching conceptual aim is therefore to open up a domain of thinking around the possibility of demarcation in our world – of our political, normative decisions, and of our reality – and to argue for the vital importance of reflection on this possibility in technological decision-making.
Modeling the Evolution of S. pombe Populations with Multiple Killer Meiotic Drivers
30860José Fabricio López Hernández, Boris Y Rubinstein, Robert L Unckless, Sarah E Zanders, G3 Genes|Genomes|Genetics, 2024-07-02 12:10:39.
Meiotic drivers are selfish genetic loci that can be transmitted to more than half of the viable gametes produced by a heterozygote. This biased transmission gives meiotic drivers an evolutionary advantage that can allow them to spread over generations until all members of a population carry the driver. This evolutionary power can also be exploited to modify natural populations using synthetic drivers known as ‘gene drives.’ Recently, it has become clear that natural drivers can spread within genomes to birth multicopy gene families. To understand intragenomic spread of drivers, we model the evolution of two or more distinct meiotic drivers in a population. We employ the wtf killer meiotic drivers from Schizosaccharomyces pombe, which are multicopy in all sequenced isolates, as models. We find that a duplicate wtf driver identical to the parent gene can spread in a population unless, or until, the original driver is fixed. When the duplicate driver diverges to be distinct from the parent gene, we find that both drivers spread to fixation under most conditions, but both drivers can be lost under some conditions. Finally, we show that stronger drivers make weaker drivers go extinct in most, but not all, polymorphic populations with absolutely linked drivers. These results reveal the strong potential for natural meiotic drive loci to duplicate and diverge within genomes. Our findings also highlight duplication potential as a factor to consider in the design of synthetic gene drives.
A New CRISPR-Driven Technology for Gene Drive in Plants
30849Lori Dajose, CalTech, 2024-06-28 11:49:31.
Spreading a specific genetic trait through a population, even if that trait does not benefit those who carry it, is the purpose of a "gene drive." Gene drives can be used for many different applications. These are divided into two broad categories: population modification and population suppression. Population modification can make mosquitos immune to, and therefore unable to spread, malaria, or make a crop more heat-tolerant in anticipation of climate change. Population suppression can be used to bring about local reduction or elimination of a weed or invasive species. But any gene editing program needs to have strict built-in controls to keep the modifications localized to a specific area and to prevent other species from accidentally inheriting modified genes. Now, Caltech researchers have developed a new gene drive technology, called ClvR (pronounced "cleaver"), that can be specifically customized to plant species, preventing accidental gene editing in cross-pollination situations. Crucially, the technology can be designed to be self-limiting, only spreading the desired genes for a limited number of generations, thereby limiting their spread in time and space. The work is the first engineered gene drive in plants and the first to enable species-specific modification as well as the first to act at the level of plant sex cells.
First synthetic gene drive for plants could help eradicate weeds
30846Erik Stokstad, Science, 2024-06-28 11:39:25.
More than a decade ago, a research group used the genome editor CRISPR to put evolution on fast forward, spurring a gene to spread throughout a population of lab-reared fruit flies many times faster than it normally could in nature. Mosquitoes with CRISPR-based “gene drives” came soon after, then mice a few years later—advances that brought a fraught mix of technological promise and ethical complexity. Proponents tout gene drives as a way to prevent insect-borne diseases, wipe out rats and other invasive creatures, and even help prevent extinction of endangered species. But one set of organisms had stood apart from the excitement: plants. Now, geneticists report that synthetic gene drives can work in flora, too. Circumventing a long-standing hurdle, two teams have independently engineered Arabidopsis thaliana, a small mustard popular for lab work, to carry a genetic payload that is inherited by up to 99% of offspring. Modeling suggests a similar gene could permeate a natural plant population in 10 to 30 generations. “What they’ve achieved is pretty amazing,” says Paul Neve, a weed scientist at the University of Copenhagen. “It is clever and innovative.”
Mosquito population structure and gene-drive
30499Heredity Podcast, 2024-06-04 20:59:37.
Gene-drives hold great potential for the control of biological pests, but first they need to be thoroughly tested under appropriate conditions. In this episode we discuss some new work assessing whether mosquito populations in Northern Australia could be used to test a gene-drive targeting malaria mosquitoes.
Where gene drive fits into WHO’s new Global Malaria Programme operational strategy
30354Mouhamed Drabo, Target Malaria, 2024-05-21 19:35:24.
On the 23rd of April 2024, WHO published an updated operational strategy for its Global Malaria Programme for the years 2024-2030. The Global Malaria Programme was initially guided by a strategy intended to cover the years 2016-2030, which served as a framework and guide for efforts to reduce the global malaria incidence and mortality rates by at least 90% within that period. Since then, a stall in progress has indicated that a different, more intensive approach needs to be taken. WHO’s updated operational strategy, notes that ‘In 2022, there were an estimated 249 million new cases of malaria worldwide, compared to 231 million in 2015.’, indicating that current efforts towards malaria elimination are not effective enough, and that the current framework, which was last revised in 2021, required for a new update.
Gene drive mosquitoes designed to eliminate malaria – but governance is complex, new film shows
29897Russell Parton, University of Exeter, 2024-05-07 16:59:05.
A radical new biotechnology could eliminate the mosquitoes that cause malaria, but in Uganda – where malaria is the leading cause of death – a lack of information and debate is undermining public debate on the issue. Professor Sarah Hartley’s new research documentary Gene Drive Mosquitoes for Malaria Control, which will be screened at Exeter Phoenix on 29 April, looks at this potentially game-changing technology through conversations with Ugandan stakeholders and explores the complexities of governance. Gene drive mosquitoes are being researched in Uganda by scientists at the Ugandan Virus Research Institute, and could soon be trialled in the wild – making Uganda one of the first countries to do so. Gene drive targets the particular genes in the malaria-transmitting female mosquito, making it unable to reproduce or transmit malaria. But unlike in other forms of genetic modification, the altered gene is inherited by more than 95% of offspring, which means the trait increases over time – allowing it to spread through a whole population. This means we could change the mosquito at a scale never seen before. Gene drive offers the possibility of controlling malaria, but the decision to release gene drive mosquitoes into the wild hinges not only on the science but on social, political and environmental issues and the support of the public.
A small-molecule approach to restore female sterility phenotype targeted by a homing suppression gene drive in the fruit pest Drosophila suzukii
29887Ma S, Ni X, Chen S, Qiao X, Xu X, Chen W, et al., PLoS Genetics, 2024-05-07 16:10:19.
CRISPR-based gene drives offer promising prospects for controlling disease-transmitting vectors and agricultural pests. A significant challenge for successful suppression-type drive is the rapid evolution of resistance alleles. One approach to mitigate the development of resistance involves targeting functionally constrained regions using multiple gRNAs. In this study, we constructed a 3-gRNA homing gene drive system targeting the recessive female fertility gene Tyrosine decarboxylase 2 (Tdc2) in Drosophila suzukii, a notorious fruit pest. Our investigation revealed only a low level of homing in the germline, but feeding octopamine restored the egg-laying defects in Tdc2 mutant females, allowing easier line maintenance than for other suppression drive targets. We tested the effectiveness of a similar system in Drosophila melanogaster and constructed additional split drive systems by introducing promoter-Cas9 transgenes to improve homing efficiency. Our findings show that genetic polymorphisms in wild populations may limit the spread of gene drive alleles, and the position effect profoundly influences Cas9 activity. Furthermore, this study highlights the potential of conditionally rescuing the female infertility caused by the gene drive, offering a valuable tool for the industrial-scale production of gene drive transgenic insects.
Genetically modified mosquitoes could one day end malaria
29553Alexis Akwagyiram, Semafor, 2024-04-25 17:31:43.
Abdoulaye Diabaté, a scientist from Burkina Faso, is at the vanguard of efforts to eliminate malaria by editing the genetic makeup of male mosquitoes and releasing them in the wild to prevent the reproduction of female mosquito species that transmit malaria. The technique is known as “gene drive” technology. Malaria kills more than 600,000 people every year, most of whom are children in Africa. Research by Diabaté, who heads medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences, earned him the 2023 Falling Walls Prize for Science and Innovation Management. He spoke to Semafor Africa ahead of a Ted Talk on ending malaria. Gene drive offers great promises as a vector control tool. The fact that it is self-sustaining, meaning that a relatively small release of modified mosquitoes are able to spread within a population and induce suppression. It allows targeting a large area in a cost effective and self-sustaining manner, reaching areas that are difficult to control with conventional methods.
Group trains Nigerian journalists on “gene drives” controversies
29550Tosin Omoniyi, Premium Times, 2024-04-25 17:23:47.
The Renevlyn Development Initiative (RDI) held a training for Nigerian journalists on the controversies surrounding the ‘gene drives’ research organisations that allegedly target Africans as “guinea pigs.” The training, the organisers said, was aimed at equipping journalists to understand the issues and be able to report the controversies robustly. The Executive Director of RDI, Philip Jakpor, in his opening remarks, said in conceiving the training, the organisation realised that the media is key not only in keeping the public informed but also in “exposing and interrogating initiatives and innovations that are extraneous to Africans and African culture as part of its watchdog role”. Gene drive is a technology that allows a chosen set of genes to alter an animal’s biology in certain ways, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the “laws of inheritance.” Specifically, the genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, scientists argue that their careful use might save millions of lives by making, for instance, 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 such a technology.
Genetic and geographic population structure in the malaria vector, Anopheles farauti, provides a candidate system for pioneering confinable gene-drive releases
29098Ambrose, L., Allen, S.L., Iro’ofa, C. et al., Heredity, 2024-04-16 09:13:44.
Indoor insecticide applications are the primary tool for reducing malaria transmission in the Solomon Archipelago, a region where Anopheles farauti is the only common malaria vector. Due to the evolution of behavioural resistance in some An. farauti populations, these applications have become less effective. New malaria control interventions are therefore needed in this region, and gene-drives provide a promising new technology. In considering developing a population-specific (local) gene-drive in An. farauti, we detail the species’ population genetic structure using microsatellites and whole mitogenomes, finding many spatially confined populations both within and between landmasses. This strong population structure suggests that An. farauti would be a useful system for developing a population-specific, confinable gene-drive for field release, where private alleles can be used as Cas9 targets. Previous work on Anopheles gambiae has used the Cardinal gene for the development of a global population replacement gene-drive. We therefore also analyse the Cardinal gene to assess whether it may be a suitable target to engineer a gene-drive for the modification of local An. farauti populations. Despite the extensive population structure observed in An. farauti for microsatellites, only one remote island population from Vanuatu contained fixed and private alleles at the Cardinal locus. Nonetheless, this study provides an initial framework for further population genomic investigations to discover high-frequency private allele targets in localized An. farauti populations. This would enable the development of gene-drive strains for modifying localised populations with minimal chance of escape and may provide a low-risk route to field trial evaluations.
Talking About Gene Drive in Uganda: The Need for Science Communication to Underpin Engagement
29082Hartley, S., Stelmach, A., Opesen, C., Openjuru, G. L., and Neema, S., Science Communication, 2024-04-04 09:15:22.
Uganda may host the world’s first field trials of gene drive mosquitoes for malaria control. Global North discourses pre-suppose African publics have access to information about gene drive and are ready to make decisions about its governance. We explore assumptions about the availability of this information in Uganda. We find a paucity of information available combined with a strong desire for information from lay publics. We discuss these findings in the context of Ugandan information infrastructures and political sensitivities to genetic technologies. If Ugandans are to decide about gene drive, they need independent information about the science to underpin engagement.
The organizational structure of global gene drive research
29047Florian Rabitz, Global Environmental Change, 84. 2024-03-19 18:00:17.
Gene drives are a proposed method for large-scale in situ genetic engineering.
Scientism, trust, value alignment, views of nature, and U.S. public opinion about gene drive mosquitos
31447Evans, J. H., & Schairer, C. E., Public Understanding of Science, 2024-03-12 21:29:22.
Gene drive could be a powerful tool for addressing problems of conservation, agriculture, and human health caused by insect and animal pests but is likely to be controversial as it involves the release of genetically modified organisms. This study examined the social determinants of opinion of gene drive. We asked a representative sample of the U.S. public to respond to a description of a hypothetical application of a gene-drive mosquito to the problem of malaria and examined the relationship of these responses with demographic and ideological beliefs. We found strong general approval for the use of gene-drive mosquitos to address malaria, coinciding with the concern about a possible environmental impact of modified mosquitos and that gene drives represent “too much power over nature.” Among the determinants we measured, respondent acceptance of scientism and trust that scientists are advancing the public’s interest were the greatest predictors of views of gene drive.
Flight Against Infections: The Role of Genetically Engineered Mosquitoes, with Dr. Stephanie James
28997EeKs on Health, YouTube, 2024-03-11 10:40:20.
In this episode of Causes or Cures, Dr. Eeks chats with Dr. Stephanie James about the potential use of genetically modified mosquitoes (GMMs) to fight diseases that mosquitoes carry and spread, such as Malaria and Dengue Fever. In the podcast, Dr. James provides an overview on GMMs, as well as what something called Gene Drive Modified Mosquitoes (GDMMs) are. She talks about the current state of research, testing, and describes the GeneConvene Global Collaborative "GeneConvene", which was created to advance best practices and informed decision making for developing GMMs and GDMMs. She talks about the potential benefits versus the potential risks, how they are conducting risk assessments, how they plan to test GMMs, the ethical and safety concerns, and how local communities will be included in the decision-making process.
CRISPR could eradicate horrific parasite that’s killing cattle
28993Kristin Houser, Freethink, 2024-03-11 10:19:23.
Uruguay is developing a CRISPR gene drive to eradicate the New World screwworm, a parasitic fly that kills cattle in a painful, grisly fashion. Releasing it into the wild would have risks, but if it works, it could help rid South America of this horrific agricultural pest. The screwworm fly lays its eggs on living creatures — often livestock — and once they hatch, the larvae eat into the animal’s flesh for about a week, before emerging from the tunnel they created and flying away. “We know that it’s horrendously painful, because people get affected by this, and the standard of treatment is you give them morphine immediately so that surgeons can cut the things out — because it’s just that painful; it’s unbelievably agonizing,” Kevin Esvelt, a biologist at the MIT Media Lab, told the 80,000 Hours podcast in 2023. Aside from being painful, screwworm infestations of livestock are incredibly costly. In the 1950s, the US meat and dairy industries were losing an estimated $200 million per year to the pests — that’d be about $2.3 billion today. Screwworms are no longer a problem for American farmers thanks to the USDA. In 1955, it set out to eradicate the screwworm in the US by irradiating the insects’ larvae, which made adults sterile. Infertile males could then be released into infested areas to mate with females, which wouldn’t produce any offspring.
Un1Cas12f1 and Cas9 gene drive in HSV1: viruses that ‘infect’ viruses
28972Qiaorui Yao, Zhuangjie Lin, Keyuan Lai, Xianying Zeng, Guanxiong Lei, Tongwen Zhang, Hongsheng Dai, bioRxiv, 2024-03-05 14:11:19.
Synthetic CRISPR-Cas9 gene drive has been developed as a potential tool to control harmful species. However, Cas9 gene drive faces high resistance rate and mitigation strategies developed so far are difficult to implement. Furthermore, studying the resistance to gene drive is time consuming and challenging in higher organisms. We here tackled these two challenges simultaneously by generating Cas9 and Un1Cas12f1 gene drive in a fast-replicating DNA virus, HSV1. We assessed the transmission dynamics and resistance formation through phenotypical staining and next-generation sequencing, and demonstrated that HSV1 supported fast and effective transmission of gene drives, and the Un1Cas12f1 gene drives yielded greater conversion and lower resistance than did the Cas9 gene drives. This positions the Un1Cas12f1 gene drive as a promising alternative, and HSV1 emerges as a dependable and swift platform for gene drive assessment. The gene drive viruses function like pathogens that specifically infect viruses, offering potential applications in attenuating viral infections.
Gene Drive Systems To Control Aedes Aegypti Mosquitoes Make Headway
28966Joshua Ang, Outreach Network for Gene Drive Research, 2024-03-05 13:15:42.
Aedes aegypti mosquitoes are known vectors of several diseases, including dengue, chikungunya, yellow fever, and Zika, which impact millions of people worldwide each year. The effectiveness of existing insecticide-based methods to control this mosquito is threatened by growing insecticide resistance, underscoring the need to develop new approaches. The advent of CRISPR/Cas9 genome editing has reshaped the research and development landscape of new potential vector control tools, leading researchers to explore novel approaches, such as gene drive technologies. In the past few years, gene drive technologies have gained remarkable traction, particularly for their success in controlling major malaria mosquito vectors in laboratory settings. A gene drive is able to bias its own inheritance, facilitating the spread of a specific trait through a target population. This super-Mendelian pattern of propagation makes gene drive technology an efficient and cost-effective potential new method to control mosquitoes that transmit disease.
Uruguay wants to use gene drives to eradicate devastating screwworms
28961Abdullahi Tsanni, MIT Technology Review, 2024-03-05 12:53:17.
On a warm, sunny day in Montevideo, Uruguay, the air is smogless and crisp. Inside a highly secured facility at the National Institute of Agricultural Research (INIA) are a sophisticated gene gun, giant microscopes, and tens of thousands of gene-edited flies, their bright blue wings fluttering against the walls of their small, white, netted cages. These flies—shown to me on video by an INIA veterinarian, Alejo Menchaca—are a new weapon that may soon be unleashed against an enemy that kills cattle and costs the livestock industry millions of dollars every year: the New World screwworm, a parasite common in parts of South America and the Caribbean. When a female screwworm fly attacks cattle, it lays eggs, which hatch and turn into worm-like larvae that screw down into the host animal, feeding on flesh along their way and damaging the animal’s skin. Left untreated, the animals eventually die in excruciating agony. But Menchaca and colleagues have a plan. Using the genome-editing system CRISPR, they’ve developed what’s known as a gene drive, a type of genetic element that manipulates the reproductive process to spread farther and faster than an ordinary gene. They are about to move into the next stage of caged trials in the lab, with a view to eventually using the genetic tool to decimate the screwworm fly population. In collaboration with Institut Pasteur de Montevideo, they have received a $450,000 grant from the Inter-American Development Bank (IDB) for the research.
Taking the fight against disease to mosquitoes
28948Gregory Devine, Setopati, 2024-02-27 18:33:30.
In the medium term it's likely that suppression strategies involving self-limiting genetic modifications, Wolbachia infection and irradiation will be extended to a small number of our most important mosquito vectors of disease.
“Mozzie Drive” Card Game rules
28945Katie Willis, Ace North, Target Malaria, 2024-02-27 18:24:27.
Mozzie Drive is an educational card game that demonstrates how gene drive technology could be used to reduce populations of malaria mosquitoes. To download the game for free, please visit: https://targetmalaria.org/why-malaria... . This game was designed by Dr. Katie Willis and Dr. Ace North from the Target Malaria modelling team.
Acetylcholine esterase of Drosophila melanogaster: a laboratory model to explore insecticide susceptibility gene drives
28938Hernandes, N., Qi, X.M., Bhide, S., Brown, C., Camm, B.J., Baxter, S.W. and Robin, C., Pest Management Science, 2024-02-27 18:08:08.
One of the proposed applications of gene drives has been to revert pesticide resistant mutations back to the ancestral susceptible state. Insecticides that have become ineffective because of the rise of resistance could have reinvigorated utility and be used to suppress pest populations again, perhaps at lower application doses. We have created a laboratory model for susceptibility gene drives that replaces field-selected resistant variants of the acetylcholine esterase (Ace) locus of Drosophila melanogaster with ancestral susceptible variants. We constructed a CRISPR/Cas9 homing drive and found that homing occurred in many genetic backgrounds with varying efficiencies. While the drive itself could not be homozygosed, it converted resistant alleles into susceptible ones and produced recessive lethal alleles that could suppress populations. Our studies provided evidence for two distinct classes of Gene Drive Resistance (GDR): rather than being mediated by the conventional Non-Homologous End-joining (NHEJ) pathway, one seemed to involve short homologous repair and the other was defined by genetic background. Additionally, we used simulations to explore a distinct application of susceptibility drives; the use of chemicals to prevent the spread of synthetic gene drives into protected areas. Insecticide susceptibility gene drives could be useful tools to control pest insects however problems with particularities of target loci and GDR will need to be overcome for them to be effective. Furthermore, realistic patterns of pest dispersal and high insecticide exposure rates would be required if susceptibility were to be useful as a ‘safety-switch’ to prevent the unwanted spread of gene drives.
Biotech Mosquitoes Can Help to Regain Ground in Fight Against Malaria
28932Florence Banoba, East News, 2024-02-27 17:59:07.
In response to the recent opinion articles that ran in the National print and online media in the last couple of days (1st and 5th February, 2024), regarding the use of GMO technology as a tool in the fight against malaria, I wish to address the writer’s broad-brush dismissal of the significance of genetic modification technologies in combating malaria. It is crucial, from the outset, to clarify a fundamental distinction overlooked in the article between Gene-drive and Self-limiting technologies in addressing this global health challenge. As rightly stated in that article, gene-drive technology refers to a genetic engineering technique that aims to spread a particular gene throughout a population at an accelerated rate. The primary objective would be to either suppress a mosquito population or reduce its ability to transmit malaria. Under this method, the introduced mosquitoes are designed to stay in the environment for long. In contrast, self-limiting technology involves the introduction of genetically modified organisms which possess traits designed to limit their population growth. This technology focuses on controlling or suppressing the modified organisms themselves.
SPOTLIGHT: Gene Drives for Malaria Elimination in Africa
28916Ifakara Health Institute, YouTube, 2024-02-20 20:05:51.
This SPOTLIGHT Series features Dr. Marceline Finda, a distinguished Research Scientist at Ifakara Health Institute. The insightful 20-minute discussion centered around the topic: "Gene Drives for Malaria Elimination in Africa."
Off the news: Gene-altered mosquitoes to the rescue
28902Star Advertiser, 2024-02-20 15:13:49.
A legal attempt to block deployment of genetically modified mosquitoes in a Maui forest was rejected in Circuit Court on Tuesday — cause for celebration among those hoping to save near-extinct species of Hawaiian honeycreepers. State and federal wildlife officials plan a staged release of sterile male (nonbiting) mosquitoes on the high slopes of Haleakala, crowding out breeding males to reduce the insect population. Fortunately, the challenge to the program failed: Only a very few Hawaiian honeycreepers remain, and warmer temperatures have allowed the deadly disease-carrying mosquitoes to infiltrate the birds’ only remaining island haven.
Opinion: A cautionary tale of experimenting with genetically modified mosquitoes in Uganda
28900Barbara Ntambirweki, The Independent, 2024-02-20 14:44:38.
The Uganda Virus Research Institute is pressing forward with gene drive technology which provides a way to rapidly, permanently, and genetically modify wild animals or plants. Gene drive organisms, are a genetically modified organism (GMO) designed to spread a genetic modification through entire populations of wild or farmed species, and are promoted as a ‘solution’ to pressing problems in the fields of public health, ecology and agriculture. The capacity of gene drives to spread and persist in the environment presents novel biosafety and socio-economic concerns for both people and biodiversity. Several research projects in Africa are advancing in their experiments to develop genetically modified ‘gene drive’ mosquitoes to release into the environment as a public health intervention to combat malaria and some are already releasing GMO mosquitoes similar to those touted by Oxitec. In Africa, Burkina Faso, Ghana, Tanzania and Uganda have allowed experimentation towards gene drive in their countries where some of these are under the auspices of Target Malaria – a consortium of research institutions led by laboratories based at Imperial College in the United Kingdom funded by Bill and Melinda Gates Foundation. In Uganda, Target Malaria has entered in partnership with the Uganda Virus Research Institute and has commenced entomological mosquito collections from field sites around Kalangala and Mukono Districts.
Revolutionary Gene Drive Could Provide Solution for Agricultural Pest Control
28877María Alejandra Trujillo, Breaking News Network, 2024-02-13 17:35:22.
The crux of the gene drive hinges on the process of sex determination in medflies. The drive effectively converts genetic females into fertile XX males, which, unlike their female counterparts, are harmless to crops. This innovative approach presents a possibility for a more environmentally friendly and cost-effective strategy to control agricultural pests—particularly those within the same group as medflies. The study was helmed by Dr. Nikolai Windbichler and Dr. Angela Meccariello of Imperial's Department of Life Sciences. Their work adds to the progressive field of gene drives, a concept that has demonstrated efficacy in laboratory settings, especially with regards to controlling populations of malaria-carrying mosquitoes. However, no gene drives have yet been released into the wild. The success of this proof-of-concept study stands as a testament to the potential of gene drives as a tool to manage agricultural pests. Dr. Meccariello, co-leader of the research, emphasized the untapped potential of gene drives in tackling pest problems in agriculture. She believes that this breakthrough could open the door to a more sustainable and economical approach to pest control.
Otago GE Wasp Project Violates International Gene Drive Agreement
28874GE-Free NZ, Scoop, 2024-02-13 17:02:02.
Professor Dearden, Otago University, has received $11 million from the Ministry of Business, Innovation and Enterprise (MBIE) to engineer wasps using gene drive technology. He is only consulting with Māori and regulators, ignoring and side-lining the views of other concerned New Zealanders. Gene Drives using gene editing CRISPR (clustered regularly interspaced short palindromic repeat) technology. This genetic engineering causes a permanent modification of the organisms genome, which is passed on to all subsequent generations. Gene drives are designed to impact reproduction or kill the developing larvae. Due to the irreversibility of gene drives, any out-crossing across species could collapse the insect ecosystems affecting pollinators and food security. The approval of this gene drive application is a worldwide concern, as it overrides the decision on gene drives being considered at a global level through the UN Convention of Biodiversity (CBD). MBIE and researchers at the University of Otago have violated the agreement to work in unison with the international community. International concern has already been raised by the project.
Gene driver flies and quantum finance: News from Imperial
28872Bryony Ravate, Hayley Dunning, Imperial College London, 2024-02-13 16:54:58.
Researchers have created the first gene drive for the Mediterranean fruit fly (medfly), a global agricultural pest affecting food production. The team was led by Dr Nikolai Windbichler and Dr Angela Meccariello at Imperial's Department of Life Sciences, and included researchers from the University of East Anglia and the Hebrew University of Jerusalem. Gene drives are genetic modifications that preferentially spread throughout a species, and which are designed to reduce the population. No gene drives have been released in the wild yet, but versions in malaria-carrying mosquitos have been shown to be highly effective in the lab. This success prompted the researchers to look at other pest species that could be susceptible to similar interventions. The team were able to target the process of sex determination in medflies, creating a gene drive that transforms genetic females into fertile but harmless XX males. The proof-of-concept demonstrates how gene drives can be applied to insect pests in the same group as medflies. Dr Meccariello said: “Our results demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.”
Transforming malaria prevention and control: the prospects and challenges of gene drive technology for mosquito management
28861Yusuf Amuda Tajudeen, Habeebullah Jayeola Oladipo, Iyiola Olatunji Oladunjoye, Muhammad Kamaldeen Oladipo, Hameedat Damilola Shittu, Imam-Fulani Abdulmumeen, Abdullateef Opeyemi Afolabi and Mona Said El-Sherbini, Annals of Medicine, 55. 2024-01-30 17:32:22.
In the era of insecticides and anti-malarial drug resistance, gene drive technology holds considerable promise for malaria control. Gene drive technology deploys genetic modifications into mosquito populations to impede their ability to transmit the malaria parasite. This can be either through the disruption of an essential mosquito gene or the association of gene drive with a desirable effector gene. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene editing tool that precisely modifies mosquito vector DNA sequences and curtails the rate of pathogen transmission. A comprehensive search was conducted in the SCOPUS and MEDLINE databases (via PubMed) until October 2023. The keywords used were related to the principles and mechanisms of gene drive technology, its advantages, and disadvantages, and its ethical and regulatory considerations in sustainable malaria eradication. The development of gene drive enables the preferential inheritance of specific genes in targeted mosquitoes, potentially obstructing the transmission of the Plasmodium parasite. This technology was also studied for the control of other vector-borne diseases such as dengue and chikungunya viruses. Despite its experimental superiority over other traditional methods such as insecticide-treated nets and insecticide sprays, the long-term dynamic interplay of mutation and resistance poses challenges for gene drive efficiency in sustainable malaria control. This commentary elucidates the underlying mechanisms and principles of gene drive technology, underscoring its promise and challenges as a novel strategy to curtail malaria prevalence. Although the release of such genetically modified mosquitoes into the natural environment would result in the eradication of the locally targeted species of mosquitoes, the complete eradication of the entire species remains questionable. Thus, the practical application raises significant ethical and regulatory concerns for further research and risk assessment, including the risk of gene drive spreading to nontarget species in the wider theatre of biodiverse species.
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.
Gene Drives: Mechanisms and Key Research, Explained
28795Julia Bauman, 60 Second Science, 2024-01-15 16:59:40.
A technical primer on CRISPR-based gene drives, which hold massive potential for mitigating the harms invoked by some species. We cover what a gene drive is, how it works at the genetic level, and summarize key safety & efficiency features developed in recent years.
Consultation on a draft National Gene Drive Policy Guide
28786Commonwealth of Australia (Department of Health and Aged Care), National Gene Technology Scheme, 2024-01-02 13:43:01.
The term gene drive is used to describe organisms which have been genetically modified to increase the rate for a particular trait to spread through a sexually reproducing population, spreading the genes or traits through a species at a faster rate than normal inheritance. An example might be a trait to increase likelihood of offspring to be female and thereby suppress the population of the targeted pest species. The concept of a gene drive is not a new one; these dominant genes – sometimes called selfish genes – are abundant in nature. However, GM gene drive organisms have the potential to be useful for addressing some of the environmental, agricultural, and public health challenges currently faced by Australia, such as conserving native populations, controlling significant exotic pests, or providing public health benefits. As an evolving technology, gene drives may pose risks that are not yet fully understood, including the potential to alter the ecosystem in unpredictable ways. These risks should be acknowledged and managed in a structured and systematic way if Australia wishes to be a future beneficiary of this technology. The Third Review (the Review) of the National Gene Technology Scheme (Scheme), endorsed by all Australian governments on 11 October 2018, recommended “clarifying, and where necessary strengthening, the mechanisms for regulating the environmental release of GM gene drive organisms in Australia” (Recommendation 7b). Review Recommendation 7b and development of the National Gene Drive Policy Guide (Policy Guide) cannot be considered in isolation.
CRISPR engineered viruses could render other viruses harmless
28784Michael Le Page, New Scientist, 2023-12-29 13:14:45.
A virus genetically engineered to spread its DNA to other viruses via CRISPR gene editing has done exactly that in tests in mice. The hope is that these viruses could alter others, such as herpes, in a way that prevents them from causing symptoms. “It’s a new technology,” says team member Marius Walter at the Fred Hutch Cancer Center in Seattle, Washington. “Can we bring it to people? That’s a long way ahead, we have a lot of work to do, but I think this is an exciting technology." This approach is known as a gene drive, when a bit of selfish DNA somehow manages to get passed down to a higher proportion of offspring than normal. This means gene drives can spread through a population even if they are disadvantageous.
Gene drives, mosquitoes, and ecosystems: An interdisciplinary approach to emerging ethical concerns
28778Ricardo D. Moreno, Luca Valera, Cristián Borgoño, Juan Carlos Castilla, José Luis Riveros, Frontiers in Environmental Science, 11. 2023-12-28 22:14:12.
Gene drives are genetic elements that in sexually reproducing organisms spread faster than those transmitted through a Mendelian fashion. Since gene drives can be engineered to modify different aspects of physiology and reproduction, they have been proposed as a new and revolutionary tool to control vector-borne diseases, particularly those transmitted by the genera Anopheles and Aedes (Culicidae), such as malaria, Dengue and Zika virus. This approach may impact on human health by lowering the transmission of such devastating diseases. However, the release of genetically modified mosquitos (or other species) into the environment raises a series of questions related to the still incipient technology and our present understanding of the complex structure and dynamics of terrestrial and aquatic ecosystems. Moreover, there are ethical concerns about human interventions in natural ecosystems that may eventually impact our way of living or the ecosystems themselves. This work is an interdisciplinary approach that analyzes from a biological, philosophical, and theological perspective the potential ecological impacts on natural environments of the release of genetically modified species, focusing on gene drive-modified mosquitos. It includes theological approach from a Catholic point of view (although it could be easily shared by other Christians) because we hold that world religions give valuable insights even though not everyone may share their groundings. We conclude that the focal problem is the relationship between humans and nature, and the release of genetically modified species may change this relationship unpredictably. However, given the complex interactions in ecosystems, new approaches such as Earth Stewardship principles could provide new and more widely accepted answers involving biological, philosophical, and theological concepts that will help engaging all relevant actors to make a better world.
Advancements in Gene Editing: Using CRISPR-Cas9 and Gene Drive Technology to Neutralize Viruses
28765Anonymous, News Directory 3, 2023-12-27 20:03:12.
Researchers from the US Fred Hutchinson Cancer Research Center recently published research results in the international academic journal “Nature” demonstrating that herpes virus type 1 (HSV-1) was neutralized using “Gene Drive” technology . Gene drive refers to a technology that changes the genes of a specific organism and affects the entire organism. The international academic journal Science said: “Scientists highly appreciate the potential of gene drive technology” and added: “It could be an opportunity to pave the way for modifying viral populations through genetic manipulation and using it as a new treatment."
Communicating Creatively About Genetically Modified Mosquitoes
28748Lorraine Gibson, Target Malaria, 2023-12-21 15:27:14.
In 2018, the Target Malaria team at Imperial College London published a landmark paper in Nature Biotechnology. The study demonstrated how gene drive mosquitoes successfully suppressed a population of wild-type malaria mosquitoes, marking a significant milestone for gene drive technology as a tool for malaria elimination. In our communications team working across Burkina Faso, Ghana, Uganda and the UK, we are exploring different, creative ways to explain the technology and its progress to the general public. By continually expanding our toolkit of science communications tools and embracing innovative approaches, we hope to bridge the gap between scientific advancements and the general public, in particular communities most affected by malaria, fostering understanding and support for our mission to combat malaria.
African scientist could wipe out malaria by editing mosquito DNA
28731Nimi Princewill, CNN, 2023-12-19 13:03:40.
Malaria is a leading cause of death in Burkina Faso, where nearly all of the West African nation’s 22 million inhabitants, especially children, are at risk of the disease, according to the World Health Organization. Malaria killed nearly 19,000 people in Burkina Faso in 2021, the most recent data from the WHO regional office for Africa showed. The disease is also one of the main causes of death in the wider African region, which shoulders the world’s largest malaria burden. Abdoulaye Diabate faced a life-threatening bout of malaria when he was just five years old. Diabate narrowly survived the mosquito-borne disease, but cousins ages three and four were not as fortunate. Diabate, who now heads medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences, is developing an innovative technique that could potentially wipe out malaria-transmitting mosquito species by altering their genes.
To End Malaria In Africa, a Scientist From Africa Invented Gene Drive Technology.
28728Salman Ahmad, CTN News, 2023-12-19 12:41:22.
Abdoulaye Diabate, a scientist from Africa, is currently working on a groundbreaking technology called ‘gene drive’ that has the potential to eradicate malaria or the mosquitoes that cause it from the continent. Diabate, who received the prestigious 2023 Falling Walls Prize for Science and Innovation Management, is developing an ingenious technique that can eliminate female mosquitoes responsible for transmitting malaria by modifying their genes. Using gene drive technology, the reproduction of female mosquitoes is hindered by releasing genetically modified male mosquitoes into the environment. This approach would result in a significant reduction in the number of female mosquitoes, thereby combating malaria throughout the continent.
Gene Drive: Engineered viruses take on their own kind in a new study
28711Rizwan Choudhury, Interesting Engineering, 2023-12-18 09:27:39.
Scientists are exploring a radical idea to combat viral infections: use viruses against themselves. They are testing whether introducing modified viruses into people with the same natural viruses can spread a gene that destroys the infection. This has yet to be done successfully in animals, but a study has shown it is possible in theory. The technique uses gene drives, tools that use CRISPR, a gene editing system, to speed up gene transmission in the offspring. Gene drives have been used to alter animals like mice and mosquitoes to reduce their numbers. But a recent study showed that gene drives can also work with herpesvirus-1 (HSV-1), which causes cold sores. When mice were infected with both normal and modified herpesviruses, the gene drive changed up to 90% of the viruses, which could prevent the infection from causing symptoms. Another study achieved similar results with HSV-1 in cells in the lab.
Gene Drive Technology Unlocks Innovative Potential Solutions At The Intersection Of Climate Change And Public Health
28705Krystal Birungi, African Media Agency, 2023-12-12 17:23:52.
The inaugural ‘Day of Health’ at the UN Climate Conference (COP-28) highlighted the dramatic impact of climate change on health, diseases and in particular on malaria. Heads of State and climate experts converged in Dubai to emphasise the indisputable link between climate and health, echoing WHO Director-General Dr. Tedros Adhanom Ghebreyesus’s statement that climate change is a pressing public health issue. As we grapple with the harsh reality of half a million lives lost annually to malaria, including a child succumbing every minute in Africa, it is imperative to integrate innovative solutions that address both the disease and its broader public health implications exacerbated by climate change.
Population suppression with dominant female-lethal alleles is boosted by homing gene drive
28685Jinyu Zhu, Jingheng Chen, Yiran Liu, Xuejiao Xu, Jackson Champer, bioRxiv, 2023-12-07 10:24:25.
Methods to suppress pest insect populations using genetic constructs and repeated releases of male homozygotes have recently been shown to be an attractive alternative to older sterile insect technique based on radiation. Female-specific lethal alleles have substantially increased power, but still require large, sustained transgenic insect releases. Gene drive alleles bias their own inheritance to spread throughout populations, potentially allowing population suppression with a single, small-size release. However, suppression drives often suffer from efficiency issues, and the most well-studied type, homing drives, tend to spread without limit. In this study, we show that coupling female-specific lethal alleles with homing gene drive allowed substantial improvement in efficiency while still retaining the self-limiting nature (and thus confinement) of a lethal allele strategy. Using a mosquito model, we show the required releases sizes for population elimination in a variety of scenarios, including different density growth curves, with comparisons to other systems. Resistance alleles reduced the power of this method, but these could be overcome by targeting an essential gene with the drive while also providing rescue. A proof-of-principle demonstration of this system in Drosophila melanogaster was effective in both basing its inheritance and achieving high lethality among females that inherit the construct in the absence of antibiotic. Overall, our study shows that substantial improvements can be achieved in female-specific lethal systems for population suppression by combining them with a gene drive.
Transformative Approaches for Sustainable Weed Management: The Power of Gene Drive and CRISPR-Cas9
28677Kumam, Y.; Trick, H.N.; Vara Prasad, P.V.; Jugulam, M., Genes, 14. 2023-12-06 13:31:23.
Weeds can negatively impact crop yields and the ecosystem’s health. While many weed management strategies have been developed and deployed, there is a greater need for the development of sustainable methods for employing integrated weed management. Gene drive systems can be used as one of the approaches to suppress the aggressive growth and reproductive behavior of weeds, although their efficacy is yet to be tested. Their popularity in insect pest management has increased, however, with the advent of CRISPR-Cas9 technology, which provides specificity and precision in editing the target gene. This review focuses on the different types of gene drive systems, including the use of CRISPR-Cas9-based systems and their success stories in pest management, while also exploring their possible applications in weed species. Factors that govern the success of a gene drive system in weeds, including the mode of reproduction, the availability of weed genome databases, and well-established transformation protocols are also discussed. Importantly, the risks associated with the release of weed populations with gene drive-bearing alleles into wild populations are also examined, along with the importance of addressing ecological consequences and ethical concerns.
Viruses that ‘infect’ viruses: Cas12f1 and Cas9 gene drive in HSV1
28673Hongsheng Dai, Qiaorui Yao, Zhuangjie Lin, Keyuan Lai, Xianyin Zeng, Guangxiong Lei, Tongwen Zhang, bioRxiv, 2023-12-06 12:08:32.
Cas9-based synthetic gene drives constitute some minimal elements capable of editing DNA with sequence specificity. However, they face high resistance rate and mitigation strategies developed so far are difficult to implement. Here, we engineered herpes simplex virus type 1 (HSV1) as a vector for gene drive, generated viruses carrying either Cas9 or Cas12f1 gene drives, and compared their performance in spreading the gene drive and causing resistance. Based on phenotypical staining and NGS sequencing, we showed that HSV1 supported fast and effective transmission of gene drive, and Cas12f1 gene drive yielded higher conversion and lower resistance than Cas9 gene drive. Cas12f1 gene drive is a promising alternative to Cas9 gene drive, and HSV1 is a reliable and fast platform to evaluate gene drive. Gene drive viruses worked like pathogens that specifically infect viruses and could potentially be used to attenuate viral infection.
A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance
28651Jingheng Chen, Shibo Hou, Ruobing Feng, Xuejiao Xu, Nan Liang, Jackson Champer, bioRxiv, 2023-12-05 10:59:48.
CRISPR homing gene drive is a potent technology with considerable potential for managing populations of medically and agriculturally significant insects. It induces a bias in the inheritance of the drive allele in progeny, rapidly spreading desired genes throughout the population. Homing drives operate by Cas9 cleavage followed by homology-directed repair, copying the drive allele to the wild-type chromosome. However, resistance alleles formed by end-joining repair pose a significant obstacle to the spread of the drive. To address this challenge, we created a homing drive targeting the essential but haplosufficient hairy gene. Our strategy involves spreading the drive construct through the homing process, eliminating nonfunctional resistance, which are recessive lethal, while rescuing drive-carrying individuals with a recoded version of hairy. This strategy eliminates resistance more slowly than a previous strategy targeting haplolethal genes, but it may be easier to construct in non-model organisms. Our drive inheritance rate was moderate, and multigenerational cage studies showed quick drive spread to 96-97% of the population. However, the drive failed to reach the whole population due to the formation of functional resistance alleles, despite use of four gRNAs, a strategy that previously was successful at preventing functional resistance. Sequencing showed that these alleles had a large deletion and must have utilized an alternate start codon. The resistance allele had a modest fitness advantage over the drive in a cage study, which could prevent long-term persistence of the drive, especially if cargo genes had an additional fitness cost. Thus, revised design strategies targeting more essential regions of a target gene may often be necessary to avoid such functional resistance, even when using multiplexed gRNAs.
ISAAA Inc. | Genetic Tools For Conservation and Health: What’s The Role of Gene Drives?
28634Kristine Grace N. Tome, Science Speaks, 2023-12-04 11:20:10.
ISAAA Inc., in partnership with the Outreach Network for Gene Drive Research and the Malaysian Biotechnology Information Centre (MABIC), gathered approximately 834 online participants during the webinar Genetic Tools for Conservation and Health: What's the Role of Gene Drives? held on November 16, 2023, via Zoom and livestreamed on Facebook and YouTube. The online session is the first of the 2023 Gene Drive Webinar Series that focuses on the interests of 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. The Philippines has been picked as the first country to be engaged in the webinar series. The Philippines has been at the forefront of biotechnology research and regulation in Asia for a long time and plays an important role in shaping the region’s views on novel technologies and developing expertise.
Invasive Feral Cats Could Be Wiped Out Using Genetic Modification
28632Jess Thomson, Newsweek, 2023-12-04 10:38:32.
Hordes of feral cats terrorizing native species in Australia could be combatted using a special type of genetic engineering, scientists have suggested. The cats, which came to Australia via European colonizers, regularly kill native mammals, birds, and reptiles, including woylies, quolls, and even penguins. The feral cats now number over six million, and are responsible for the extinction of at least 28 species across the country, threatening countless more. This has spurred numerous control measures to be announced, including poison, trapping, and cat curfews. "Gene drives literally 'drive' modified genes through a species by ensuring they are inherited from generation to generation, eventually resulting in the whole species having engineered genetic traits," Andrew D. Maynard, a professor of Advanced Technology Transitions at Arizona State University, told Newsweek. "It's a technique that is specific to species that mate and reproduce sexually, and works by ensuring that engineered genetic traits are inherited by every single offspring resulting from mating."
Food for thought: Assessing the consumer welfare impacts of deploying irreversible, landscape-scale biotechnologies
28628Michael S. Jones, Zachary S. Brown, Food Policy, 121. 2023-12-04 10:24:17.
Genetically engineered insects have gained attention as regionally deployed pest control technologies, with substantial applications in agriculture for combatting intractable crop pests and diseases. One potential tool is a ‘gene drive’, using CRISPR-based gene editing. In gene drive, preferentially inherited, engineered traits are spread throughout a geographic area to reduce pest populations or inhibit disease transmission, while also potentially reducing pesticide use and crop prices. But the self-perpetuating nature of gene drives presents a consequence, in that consumers could eventually be limited to only host crops grown in the presence of these genetically engineered insects. In this study, we analyze potential consumer welfare impacts of these technologies using discrete choice experiment data from a representative sample of U.S. adults, examining preferences regarding gene drive use to control spotted wing drosophila in blueberries and Asian citrus psyllid in orange juice (OJ) production. We find smaller average discounts for gene drives versus increased conventional pesticide use or genetically modified crops. Only 27% and 25% of blueberry and OJ consumers, respectively, are estimated to derive disutility from gene drives. However, gene drive disutility for these consumers is so large that elimination of non-drive options from their choice sets results in negative (blueberries) or neutral (OJ) effects to aggregate consumer welfare when weighed against gains to other consumers from reduced prices. Positive welfare effects are recovered by retaining availability of non-gene-drive products. We argue that this type of analysis will be increasingly important as landscape-level biotechnologies are deployed to address challenges to agricultural sustainability.
Manipulating the Destiny of Wild Populations Using CRISPR
28626Raban R, Marshall JM, Hay BA, Akbari OS., Annual Reviews, 57:361-390. 2023-12-04 09:57:57.
Genetic biocontrol aims to suppress or modify populations of species to protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge in research in this field, with one gene editing technology, CRISPR, leading the charge. This review focuses on the current state of CRISPR technologies for genetic biocontrol of pests and highlights the progress and ongoing challenges of using these approaches.
What are gene drives, and how can they help eradicate invasive species in Australia?
28563Dr. Ellen Cottingham, ABC News (Australia Broadcasting Corporation), 2023-11-29 13:52:33.
The impact of feral cats and other invasive species is felt across Australia. Not only do they threaten native species, but they can also spread diseases to humans and livestock. Invasive species are estimated to cost Australia an eye-watering $25 billion annually, while the global cost is a staggering $423 billion. Feral cats are everywhere — the nation is home to up to 6.3 million of them, and they are responsible for killing millions of native mammals, reptiles, and birds each day. Minister for the Environment and Water Tanya Plibersek recently declared "war on feral cats", announcing plans involving cat curfews, desexing regulations, and caps on cat numbers in homes. But what can we do about the millions of feral cats already wreaking havoc across Australia? And what about other pests such as foxes, rabbits, cane toads, carp, pigs, deer, or goats? One technique with the potential to help fight not just cats but all invasive species is called a "gene drive".
Repeat mediated excision of gene drive elements for restoring wild-type populations
28543Pratima R Chennuri, Josef Zapletal, Raquel D Monfardini, Martial Loth Ndeffo-Mbah, Zach N Adelman, Kevin M Myles, bioRxiv, 2023-11-28 11:32:14.
We demonstrate here that single strand annealing (SSA) repair can be co-opted for the precise autocatalytic excision of a drive element. Although SSA is not the predominant form of DNA repair in eukaryotic organisms, we increased the likelihood of its use by engineering direct repeats at sites flanking the drive allele, and then introducing a double-strand DNA break (DSB) at a second endonuclease target site encoded within the drive allele. We have termed this technology Repeat Mediated Excision of a Drive Element (ReMEDE). Incorporation of ReMEDE into the previously described mutagenic chain reaction (MCR) gene drive, targeting the yellow gene of Drosophila melanogaster, replaced drive alleles with wild-type alleles demonstrating proof-of-principle. Although the ReMEDE system requires further research and development, the technology has a number of attractive features as a gene drive mitigation strategy, chief among these the potential to restore a wild-type population without releasing additional transgenic organisms or large-scale environmental engineering efforts.
Mosquito modification programme aiming to eliminate malaria receives US$15m
28402Hayley Dunning, Imperial College London, 2023-11-14 15:15:02.
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 bites from Anopheles mosquitoes. 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. With current measures failing to halt disease transmission, new ways to control the spread of malaria are desperately needed. Transmission Zero is a global programme led by scientists at Imperial College London (Imperial) and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), which aims to modify specific species of mosquitoes so that they are unable to transmit the disease.
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.
Gene Drive Mosquitoes from Islamic Perspective: A Preliminary Discussion
28385N. M. Isa, Global Journal Al-Thaqafah, 13. 2023-11-11 10:14:15.
Gene drive mosquitoes could spread desired trait, such as female infertility within a wild population at a rate higher than the normal inheritance rate and could eventually wipe out the population. Consequently, this makes gene drive mosquitoes one of the promising approaches in controlling mosquito-borne diseases, such as malaria and dengue. Despite its potentials, the development of gene drive mosquitoes has raised ethical concerns, mainly on the issues of safety and efficacy, as well as tampering with nature. Little research has been conducted to explore religious perspectives on this new advancement. This article aims to fill that gap by exploring the ethics of gene drive mosquitoes from Islamic perspectives. This article outlines three aspects, namely the purposes, the potential benefits and harms, and the need of the technology that should be considered when discussing whether gene drive mosquitoes should be allowed from Islamic perspectives. © (2023), (Universiti Sultan Azlan Shah). All Rights Reserved.
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.
Current Status of the Main Olive Pests: Useful Integrated Pest Management Strategies and Genetic Tools
28380E. Lantero, B. Matallanas and C. Callejas, Applied Sciences, 13. 2023-11-06 09:55:38.
Mediterranean olive cultivation faces challenges in the global environmental change context. Pests and diseases caused by arthropods such as Bactrocera oleae, Prays oleae, and certain vectors of Xylella fastidiosa are expected to increase and spread in part due to this global scenario. The control of these arthropods has relied on synthetic pesticides, the misuse of which has led to pest population resistance and concerns about their negative impacts on biodiversity and global health. Integrated pest management (IPM) methods have emerged through the careful consideration of all available control techniques and the subsequent integration of appropriate measures that discourage the development of pest populations. This paper reviews the IPM guidelines for olive cultivation, prioritizing the use of biological control methods, and the integration of genetics and biotechnology, which bring precision, efficacy, and safety. It evidences the importance of genetic analysis in pest populations, pesticide resistance and in the contributions of predators to pest control. Advances in formulations and delivery systems for pesticides such as Bacillus thuringiensis, plant-incorporated protectants, improved SIT techniques, and the specific efficacy of biologicals pesticides are covered. Finally, this paper explores promising tools such as RNAi and gene drive while recognizing the ethical, environmental, and regulatory challenges associated with their use. Shortly, these innovations have the potential to reduce the environmental impacts of pests while ensuring the long-term viability of the olive industry.
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.
Quantifying Fitness Costs in Transgenic Aedes aegypti Mosquitoes
27981I. Sanchez-Vargas, A. E. Williams, L. E. Martin, I. Martin-Martin, S. Bennett, K. E. Olson and E. Calvo, Journal of Visualized Experiments, 2023-09-15 07:51:42.
Transgenic mosquitoes often display fitness costs compared to their wild-type counterparts. In this regard, fitness cost studies involve collecting life parameter data from genetically modified mosquitoes and comparing them to mosquitoes lacking transgenes from the same genetic background. This manuscript illustrates how to measure common life history traits in the mosquito Aedes aegypti, including fecundity, wing size and shape, fertility, sex ratio, viability, development times, male contribution, and adult longevity. These parameters were chosen because they reflect reproductive success, are simple to measure, and are commonly reported in the literature. The representative results quantify fitness costs associated with either a gene knock-out or a single insertion of a gene drive element. Standardizing how life parameter data are collected is important because such data may be used to compare the health of transgenic mosquitoes generated across studies or to model the transgene fixation rate in a simulated wild-type mosquito population. Although this protocol is specific for transgenic Aedes aegypti, the protocol may also be used for other mosquito species or other experimental treatment conditions, with the caveat that certain biological contexts may require special adaptations.
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).
Baker: New tools can change mosquitoes’ DNA, but should it be done?
27597K. Baker, Fremont News Messenger, 2023-08-09 06:54:53.
Suppose Sauron — or perhaps Gandalf — were to offer you a magical golden ring with the power to rid the world of mosquitoes once and for all. And with their demise, to save countless human lives from the many diseases for which mosquitoes are the sole or primary vectors: Malaria, dengue, West Nile virus, chikungunya, yellow fever, filariasis, tularemia, encephalitis, Zika fever, Keystone Virus, Rift Valley Fever…And not just mosquitoes. From within the folds of his cloak the wizard draws out an array of equally luminous rings with the power to cure genetic disorders like cystic fibrosis, hemophilia, and Down’s syndrome, to rid cities of mice and rats, and free the world’s farms of weeds and insect pests without the use of pesticides. Would you take them? Those rings exist and are now being refined and tested in the Elvin forges of academic, commercial, and government research facilities around the world. They go by various names, but collectively may be referred to as CRISPR-Cas Genome Editing Systems.
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.
Fighting the battle against evolution: designing genetically modified organisms for evolutionary stability
28008M. Arbel-Groissman, I. Menuhin-Gruman, D. Naki, S. Bergman and T. Tuller, Trends in Biotechnology, 2023-07-12 06:48:15.
Synthetic biology has made significant progress in many areas, but a major challenge that has received limited attention is the evolutionary stability of synthetic constructs made of heterologous genes. The expression of these constructs in microorganisms, that is, production of proteins that are not necessary for the organism, is a metabolic burden, leading to a decrease in relative fitness and make the synthetic constructs unstable over time. This is a significant concern for the synthetic biology community, particularly when it comes to bringing this technology out of the laboratory. In this review, we discuss the issue of evolutionary stability in synthetic biology and review the available tools to address this challenge
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.
Regulation of gene drive technologies for malaria control & elimination
33083Ifakara Health Institute, 2023-05-16 13:15:08.
The video talks about the importance of ensuring effective and thoughtful community and stakeholder engagement throughout research, development and deployment of gene drives for malaria control.
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.
Editorial: Genetic control of insect pest species—achievements, challenges, and perspectives
25423I. Häcker, D. Bartsch, A. Choo and F. Marec, Frontiers in Bioengineering and Biotechnology, 11. 2023-05-05 08:12:07.
Genetic control is a type ofbiological control and a promising approach to regulate insect pest populations in a species-specific manner. It is based on targeting the reproductive capacity of the target pest species to reduce population size to non-critical levels. The best known and also very successful genetic control strategy is the Sterile Insect Technique (SIT), which entails the continuous mass-release ofirradiation-sterilized males ofa given species to produce infertile matings in the field, leading to the decline in the target population over time. To date, SIT is only available for a few species, as its transfer to new target species is challenging and time consuming. Key aspects of this classical SIT and challenges in applying it to new pest species include mass rearing of target species, mass removal of female insects prior to irradiation and release, the sterilization procedure, and the biological quality control of the sterile insects produced. Besides this classical SIT strategy, current research efforts are also focused on the development of genetic control approaches based on transgenic, symbiont-mediated, or gene-drive strategies. Modern genetic technologies offer new solutions for the improvement of existing genetic control strategies and insect strains, for faster and easier transfer of existing strategies to new target species, and also for the development of new genetic control approaches. Publications within this Research Topic address pressing questions and challenges related to the genetic control of insect pests.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
25098N. de Graeff, I. Pirson, R. van der Graaf, A. L. Bredenoord and K. R. Jongsma, Bioethics, 2023-05-03 10:11:03.
Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this "community" should be defined and delineated. In this paper, we shed light on this "boundary problem": the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.
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.
Moving beyond narrow definitions of gene drive: Diverse perspectives and frames enable substantive dialogue among science and humanities teachers in the United States and United Kingdom
24692S. Hartley, A. Stelmach, J. A. Delborne and S. K. Barnhill-Dilling, Public Understanding of Science, 2023-02-06 08:31:02.
Gene drive is an emerging biotechnology with applications in global health, conservation and agriculture. Scientists are preparing for field trials, triggering debate about when and how to release gene-drive organisms. These decisions depend on public understandings of gene drive, which are shaped by language. While some studies on gene drive communication assume the need to persuade publics of expert definitions of gene drive, we highlight the importance of meaning-making in communication and engagement. We conducted focus groups with humanities and science teachers in the United Kingdom and United States to explore how different media framings stimulated discussions of gene drive. We found diversity in the value of these framings for public debate. Interestingly, the definition favoured by gene drive scientists was the least popular among participants. Rather than carefully curating language, we need opportunities for publics to make sense and negotiate the meanings of a technology on their own terms.
How CRISPR could help save crops from devastation caused by pests
24675E. F. Merchant, MIT Technology Review, 2023-02-02 10:23:26.
Researchers are now looking to add cutting-edge technology to California’s anti-Pierce’s arsenal, by changing the genome of the glassy-winged sharpshooter so that it can no longer spread the bacterium. Such a solution is possible thanks to CRISPR gene-editing technology, which has made modifying the genes of any organism increasingly simple. The technique has been used in experiments in cancer immunotherapy, apple breeding, and—controversially—human embryos. Now a growing number of researchers are applying it to agricultural pests, aiming to control a range of insects that together destroy about 40% of global crop production each year. If successful, these efforts could reduce reliance on insecticides and provide an alternative to genetic modifications to crops. For now, these gene-edited insects are shut away in labs across the globe, but that is poised to change. This year, a US company expects to start greenhouse tests in conjunction with the US Department of Agriculture (USDA) of fruit-damaging insects made sterile using CRISPR. At the same time, scientists at government and private institutions are beginning to learn more about pest genetics and to make edits in more species.
Horizontal gene transfer from plant to whitefly
24810T. Islam, R. B. Azad, S. H. Kasfy, A. A. Rahman and T. Z. Khan, Trends in Biotechnology, 2023-02-02 10:00:00.
The recent discovery of the horizontal transfer of a toxin-neutralizing gene from plant to whitefly (Bemisia tabaci), a polyphagous insect, sparked a new area of study. In this forum, we discuss some potential biotechnological applications of this newly discovered knowledge in the coevolutionary arms race between plants and whitefly.
Imperial startup Biocentis to develop genetic tech to control harmful insects
24673D. Silverman, Imperial College London, 2023-02-01 10:17:53.
The Imperial startup was founded in 2022 by Imperial researchers in partnership with technology-focused investment group Neurone to create a more effective and sustainable alternative to pesticides. While insects play an essential role in the global ecosystem, among the planet’s millions of insect species are some that spread devastating human diseases such as Dengue Fever and Zika virus, exacerbate food insecurity by spoiling up to 25% of crops, and reduce biodiversity by invading new ecosystems to the detriment of local species. At present, these harmful insect populations are controlled primarily with pesticides. But the growth of pesticide resistance is prompting control programmes to increase the dose and frequency of the toxic chemicals, causing increasing harm to bees and other non-target species.
Ethical dilemma: Should we get rid of mosquitoes?
24650Talya Hackett, TED-Ed, 2023-01-30 09:59:15.
Mosquitoes are responsible for more human deaths every year than any other animal, but very few of the 3,500 mosquito species actually transmit deadly diseases to humans. Scientists have been conducting experiments using engineered technologies called gene drives that could theoretically get rid of the most lethal mosquitoes. So, should we eradicate these pesky insects? Talya Hackett investigates.
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.
Trust in science and scientists: Effects of social attitudes and motivations on views regarding climate change, vaccines and gene drive technology
24622H. G. W. Dixson, A. F. Komugabe-Dixson, F. Medvecky, J. Balanovic, H. Thygesen and E. A. MacDonald, Journal of Trust Research, 2023-01-10 09:31:54.
Trust in science and scientists (TSS) is an increasingly important topic with respect to how science is applied within society. However, its role regarding specific issues may vary depending upon other psychosocial factors. In this study, we investigated how trust interacts with social attitudes and motivations to shape views on scientific issues in New Zealand (N = 8,199; 74.7% New Zealand European, 55.1% female). The study went beyond TSS by including broader institutional trust alongside measures relating to support for inequality, status quo preservation and fear of the unknown. We focused on their effects on three issues: vaccines, climate change and genetic technology (gene drive). Although TSS was strongly associated with lower vaccine skepticism (B = -0.497, p < 0.01), and moderate support for gene drive (B = 0.231, p < 0.01), it had no meaningful effect on climate skepticism. Furthermore, trust differentially mediated the relationship between social motivations and responses to all three issues. Trust in science and scientists is therefore unlikely to represent a one-size-fits-all variable. We conclude that future research should consider what effects trust in institutions and TSS have with social attitudes and motivations over a range of technologies across the sciences.
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.
Genes drive organisms and slippery slopes
24322D. B. Resnik, R. F. Medina, F. Gould, G. Church and J. Kuzma, Pathog Glob Health, 2022-12-22 08:58:12.
The bioethical debate about using gene drives to alter or eradicate wild populations has focused mostly on issues concerning short-term risk assessment and management, governance and oversight, and public and community engagement, but has not examined big-picture- 'where is this going?'-questions in great depth. In other areas of bioethical controversy, big-picture questions often enter the public forum via slippery slope arguments. Given the incredible potential of gene drive organisms to alter the Earth's biota, it is somewhat surprising that slippery slope arguments have not played a more prominent role in ethical and policy debates about these emerging technologies. In this article, we examine a type of slippery slope argument against using gene drives to alter or suppress wild pest populations and consider whether it has a role to play in ethical and policy debates. Although we conclude that this argument does not provide compelling reasons for banning the use of gene drives in wild pest populations, we believe that it still has value as a morally instructive cautionary narrative that can motivate scientists, ethicists, and members of the public to think more clearly about appropriate vs. inappropriate uses of gene drive technologies, the long-term and cumulative and emergent risks of using gene drives in wild populations, and steps that can be taken to manage these risks, such as protecting wilderness areas where people can enjoy life forms that have not been genetically engineered.
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.
No Environmental Release of Gene Drive Organisms
24114Anonymous, STOP GENE DRIVES, 2022-11-30 09:32:55.
We urge governments to prevent the environmental release of gene drive organisms and to establish a global moratorium on the release of gene drive organisms at the UN Convention on Biological Diversity (CBD). Gene drives work against natural rules of inheritance forcing nearly 100% instead of the usual 50% of offspring to inherit their genetically engineered traits. Whereas existing biosafety systems are designed to limit the spread and persistence of living modified organisms to mitigate against adverse impacts, gene drives are intended to spread genetic modifications to alter species and ecosystems. This would undermine the integrity of the UN Cartagena Protocol and international and national biosafety systems, including the procedures for Advanced Informed Agreement (AIA) of countries and Free, Prior and Informed consent (FPIC) of Indigenous Peoples and local communities.
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.
Gene drive technology to suppress invasive mice
23843University of Adelaide, Phys Org, 2022-11-09 09:55:57.
Researchers at the University of Adelaide have released their first findings on the potential effectiveness of revolutionary gene drive technology to control invasive mice. The team has developed a world-first proof of concept for the technology—called t-CRISPR—using laboratory mice. Using sophisticated computer modeling performed by co-first author Dr. Aysegul Birand, the researchers also found about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. The results of the study have been published today in Proceedings of the National Academy of Sciences.
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
Gene drive technologies: navigating the ethical landscape
24074N. d. Graeff, Utrecht University, 2022-11-04 10:41:56.
Gene drives are technologies that modify a particular genetic element in animals or insects so that this genetic element does not follow the typical rules of heredity, and is passed onto future generations with an increased likelihood. Gene drive technologies could be used to tackle intractable problems such as vector-borne diseases like malaria or the biodiversity impact of invasive species. At the same time, the development and governance of gene drives raise a range of ethical questions and concerns that warrant proactive ethical evaluation. In the PhD thesis ?Gene drive technologies: navigating the ethical landscape?, Nienke de Graeff analyzes these questions and concerns. In Part I, she outlines the ?ethical landscape? of gene drive technologies by identifying the associated ethical challenges through literature review and empirical ethical research. Important challenges concern how the uncertainty and risks of these technologies should be navigated, whether it is morally permissible to intervene in nature in this way, and how the development, governance, and potential deployment of gene drive technologies should be guided. In Part II, De Graeff normatively analyzes various of these challenges and provides guidance to navigate them. In Part III, she stipulates recommendations for researchers and policymakers in the gene drive field as well as lessons learned for ethics parallel research as an approach for early ethical guidance of new and emerging technologies more generally.
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.
Natural selfish genetic elements should not be defined as gene drives
23435M. A. Wells and R. A. Steinbrecher, Proceedings of the National Academy of Sciences, 119:e2201142119. 2022-08-16 07:53:39.
Gene drives are increasingly discussed in the political realm,and how the term is defined therefore has important impli-cations. The opinion piece from Alphey et al. (1) identifies alack of consensus on the definition and makes explicitchanges in how the terminology is being used by someresearchers. As such it is a timely invitation for debate.The definition of the term“gene drive”Alphey et al. (1)propose would include naturally occurring selfish geneticelements (SGEs) and natural processes causing biasedinheritance. We disagree with this aspect of the proposal,which does not reflect the original use of the term, whichrelated to engineered system
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
Manipulating Insect Sex Determination Pathways for Genetic Pest Management: Opportunities and Challenges
23084A. Siddall, T. Harvey-Samuel, T. Chapman and P. T. Leftwich, Frontiers in Bioengineering and Biotechnology, 10. 2022-06-28 07:14:08.
Sex determination pathways in insects are generally characterised by an upstream primary signal, which is highly variable across species, and that regulates the splicing of a suite of downstream but highly-conserved genes (transformer, doublesex and fruitless). In turn, these downstream genes then regulate the expression of sex-specific characteristics in males and females. Identification of sex determination pathways has and continues to be, a critical component of insect population suppression technologies. For example, “first-generation” transgenic technologies such as fsRIDL (Female-Specific Release of Insects carrying Dominant Lethals) enabled efficient selective removal of females from a target population as a significant improvement on the sterile insect technique (SIT). Second-generation technologies such as CRISPR/Cas9 homing gene drives and precision-guided SIT (pgSIT) have used gene editing technologies to manipulate sex determination genes in vivo. The development of future, third-generation control technologies, such as Y-linked drives, (female to male) sex-reversal, or X-shredding, will require additional knowledge of aspects of sexual development, including a deeper understanding of the nature of primary signals and dosage compensation. This review shows how knowledge of sex determination in target pest species is fundamental to all phases of the development of control technologies.
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 fight against malaria
22445F. Ammache, Year 2049, 2022-05-06 08:51:20.
Malaria is a disease we’ve been dealing with for thousands of years. Traces of the malaria parasite have been found in the remains of Egyptian mummies. Hippocrates described the fevers caused by malaria in Ancient Greece. The mosquito-filled Pontine Marshes protected Ancient Rome from invaders. Back then, we thought the disease was caused by people breathing “bad air”, or “mal aria”. The relationship between mosquitoes and malaria was unknown. Plasmodium falciparum, the deadliest form of malaria, was introduced by a new breed of mosquitoes around the 5th century. Some historians speculate that P. falciparum played a key role in the fall of the Roman Empire. It wasn’t until 1897 that we understood that mosquitoes transmitted malaria. Sir Ronald Ross, a British doctor based in India, found the malaria parasite in the blood of Anopheles mosquitoes which proved a hypothesis that was first put forward by his predecessor Alphonse Laveran.
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.
Podcast: How do you solve a problem like malaria?
21655A. Jha, The Economist, 2022-04-05 15:01:14.
SQUASHING MALARIA could, over the next three decades, save as many lives as covid-19 has taken. We explore new ways to fight infections: from the introduction of the first malaria vaccines, to genetically modified mosquitoes
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.”
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 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.
IMPACTOS AMBIENTAIS DA TÉCNICA DE GENE DRIVE PARA O CONTROLE DE EPIDEMIAS: ALCANCES E LIMITES DO PRINCÍPIO DA PRECAUÇÃO
23875N. R. Furtado, PERI Revista de Filosofia, 13. 2022-01-19 09:24:19.
The paper discusses the application of the precautionary principle in the management of environmental risks arising from the use of gene drives to control epidemics. Gene drives consist of a technique for creating genetically modified organisms, which are released into an ecosystem with the aim of spreading certain genetic elements and prevailing over native organisms. Among the possible uses of this technique are the control of epidemics. Despite its benefits, assessing the impact of gene drives on the environment proves to be a challenge. In the field of biotechnology, the socalled precautionary principle was formulated as a strategy to ground decisions whose consequences are uncertain. However, its application raises discussions about the ability to prevent damage from new technologies. Its critics argue that the precautionary mentality could lead to inaction, obstructing scientific development. Thus, this article highlights the contributions of such principle to guide the use of gene drives, while reflecting on its limits, confronting it with an alternative risk management model: the proactionary principle.
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.
Public Deliberation about Gene Editing in the Wild
19648M. K. Gusmano, G. E. Kaebnick, K. J. Maschke, C. P. Neuhaus and B. C. Wills, Hastings Center Report, 51 Suppl 2:S2-s10. 2021-12-14 18:42:52.
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.
Empowering Indigenous Knowledge in Deliberations on Gene Editing in the Wild
19646R. Taitingfong and A. Ullah, Hastings Center Report, 51 Suppl 2:S74-s84. 2021-12-14 18:38:07.
Proposals to release genetically engineered organisms in the wild raise complex ethical issues related to their safe and equitable implementation. While there is broad agreement that community and public engagement is vital to decision-making in this context, more discussion is needed about who should be engaged in such activities and in what ways. This article identifies Indigenous peoples as key stakeholders in decisions about gene-editing in the wild and argues that engagement activities need not only include Indigenous peoples but also be designed, conducted, and analyzed in ways that confront longstanding power imbalances that dismiss Indigenous expertise. We offer specific recommendations to guide deliberative activities to not only be inclusive of Indigenous peoples but also to empower their diverse, situated knowledges. We call on those committed to the inclusive design of broad public deliberation to pursue strategies that shift dominant power dynamics to include Indigenous communities in more meaningful ways.
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.
Mosquito transgenesis for malaria control
18284S. Dong, Y. Dong, M. L. Simões and G. Dimopoulos, Trends in Parasitology, 2021-09-02 14:42:32.
Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies.
GeneConvene Global Collaborative Webinar Series | Invasive Species Management: Informing Gene Drive Considerations
19307David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2021-08-07 13:38:24.
The management, control and elimination of invasive species involves solving problems that have analogs to those anticipating the use of gene drive technologies to control and eliminate malaria in Africa. Avoiding unintended consequences from interventions designed to reduce or remove a species from an ecosystem has parallels in some applications of gene drive technologies. Monitoring and surveilling for the movement of invasive species is critical for making management decisions and methods and approaches that have been devised to deal with challenges such as large geographic areas, low species densities, limited resources to name just a few could inform thinking about monitoring and surveillance of gene drive-containing organisms. This series of webinars by invasive species specialists will feature research into how these challenges are being successfully addressed.
Horizontal Transmission of the Symbiont Microsporidia MB in Anopheles arabiensis
17856G. Nattoh, T. Maina, E. E. Makhulu, L. Mbaisi, E. Mararo, F. G. Otieno, T. Bukhari, T. O. Onchuru, E. Teal, J. Paredes, J. L. Bargul, D. M. Mburu, E. A. Onyango, G. Magoma, S. P. Sinkins and J. K. Herren, Frontiers in Microbiology, 12. 2021-07-28 13:43:29.
The recently discovered Anopheles symbiont, Microsporidia MB, has a strong malaria transmission-blocking phenotype in Anopheles arabiensis, the predominant Anopheles gambiae species complex member in many active transmission areas in eastern Africa. The ability of Microsporidia MB to block Plasmodium transmission together with vertical transmission and avirulence makes it a candidate for the development of a symbiont-based malaria transmission blocking strategy. We investigate the characteristics and efficiencies of Microsporidia MB transmission between An. arabiensis mosquitoes. We show that Microsporidia MB is not transmitted between larvae but is effectively transmitted horizontally between adult mosquitoes. Notably, Microsporidia MB was only found to be transmitted between male and female An. arabiensis, suggesting sexual horizontal transmission. In addition, Microsporidia MB cells were observed infecting the An. arabiensis ejaculatory duct. Female An. arabiensis that acquire Microsporidia MB horizontally are able to transmit the symbiont vertically to their offspring. We also investigate the possibility that Microsporidia MB can infect alternate hosts that live in the same habitats as their An. arabiensis hosts, but find no other non-anopheline hosts. Notably, Microsporidia MB infections were found in another primary malaria African vector, Anopheles funestus s.s. The finding that Microsporidia MB can be transmitted horizontally is relevant for the development of dissemination strategies to control malaria that are based on the targeted release of Microsporidia MB infected Anopheles mosquitoes.
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.
The legal regulation of gene drive technologies
16914C. Elves, Univeristy of Oxford, 2021-05-01 13:32:03.
Gene drive technologies purport to provide a panacea and yet in doing so present unprecedented risks that threaten to change, potentially irreversibly, the way in which we live in the world. Gene drive technologies raise questions about what ends societies ought to seek for their citizens, how they are constituted and how those ends might be attained. Despite this, current discussions surrounding gene drive technologies and their regulation focus almost exclusively on the technical implications. Drawing on the work of sociologists and STS scholars, this thesis argues that lawyers ought to think critically about the ways in which they go about developing their understandings of new technologies as regulatory objects. Lawyers need to evaluate and scrutinize the knowledge claims with which they are presented, and work to identify those extending beyond the required technical expertise, if the regulatory frames they build are to bear fidelity to the realities of the technology. This thesis draws out the regulatory disconnection generated by the current regulation of gene drive technologies through the existing European Union GMO regime. It then goes on to describe the ways in which regulatory reconnection might be achieved by constructing broader frames through which we describe gene drive technologies as a regulatory object. In thinking about how lawyers might go about broadening the frames that they build, this thesis takes examples from Public Health Law scholarship and legislation. In response to both the normative and epistemic lacunae highlighted above, this thesis develops an account of why and how ethical enquiry ought to play a significant role in informing our descriptions of gene drive technologies as regulatory objects. Furthermore, this thesis argues that ethical enquiry is capable of articulating questions to which technical experts must provide answers if we are to develop fuller understandings of the technologies we regulate. In this way, ethical enquiry can help lawyers bridge both the normative and epistemic gaps that they are so often faced with in the regulation of emerging technologies.
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?
How do local communities participate in gene drive research?
16680Outreach Network for Gene Drive Research, 2021-04-12 14:39:00.
How do local communities participate in gene drive research?
ReMOT Control Delivery of CRISPR-Cas9 Ribonucleoprotein Complex to Induce Germline Mutagenesis in the Disease Vector Mosquitoes Culex pipiens pallens (Diptera: Culicidae)
17482X. X. Li, Y. Xu, H. B. Zhang, H. T. Yin, D. Zhou, Y. Sun, L. Ma, B. Shen and C. L. Zhu, Journal of Medical Entomology, 58. 2021-02-16 14:57:35.
The wide distribution of Culex (Cx.) pipiens complex mosquitoes makes it difficult to prevent the transmission of mosquito-borne diseases in humans. Gene editing using CRISPR/Cas9 is an effective technique with the potential to solve the growing problem of mosquito-borne diseases. This study uses the ReMOT Control technique in Culex pipiens pallens (L.) to produce genetically modified mosquitoes. A microinjection system was established by injecting 60 adult female mosquitoes-14 mu l injection mixture was required, and no precipitation occurred with <= 1 mu l of endosomal release reagents (chloroquine or saponin). The efficiency of delivery of the P2C-enhanced green fluorescent protein-Cas9 (P2C-EGFP-Cas9) ribonucleoprotein complex into the ovary was 100% when injected at 24 h post-bloodmeal (the peak of vitellogenesis). Using this method for KMO knockout, we found that gene editing in the ovary could also occur when P2C-Cas9 RNP complex was injected into the hemolymph of adult Cx. pipiens pallens by ReMOT Control. In the chloroquine group, of the 2,251 G(0) progeny screened, 9 individuals showed with white and mosaic eye phenotypes. In the saponin group, of the 2,462 G(0) progeny screened, 8 mutant individuals were observed. Sequencing results showed 13 bp deletions, further confirming the fact that gene editing occurred. In conclusion, the successful application of ReMOT Control in Cx. pipiens pallens not only provides the basic parameters (injection parameters and injection time) for this method but also facilitates the study of mosquito biology and control.
Playing God and tampering with nature: popular labels for real concerns in synthetic biology
16201L. Carter, A. Mankad, E. V. Hobman and N. B. Porter, Transgenic Research, 2021-01-27 15:26:41.
We present the findings from a large Australian study (N = 4593) which suggests ‘playing God’ objections and their variants can be multilayered and, at times, accompanied by meaningful information about risk perceptions. We use qualitative analysis of ope
His Passion Was Contagious
15928D. C. McCool, Notre Dame Magazine, 2021-01-01 19:03:35.
Craig was an entomologist and vector biologist whose interest in mosquitoes and the diseases they transmit to people was as contagious as the pathogens themselves. Hesburgh could not have chosen a more driven faculty member. In his 38 years at Notre Dame, before he died in 1995 at an Entomology Society of America conference in Las Vegas, Craig cultivated a legacy in a field that was in its infancy. His personality attracted even more people dedicated to eliminating mosquito-borne diseases, and the circle widened in unexpected ways. The Chicago native directed more than 40 doctoral students and mentored 38 postdoctoral researchers. He created Notre Dame’s Vector Biology Laboratory — vectors pass diseases from one organism to another — with a focus on the Aedes genus of mosquitoes. He became Notre Dame’s first member of the prestigious National Academy of Sciences (NAS). And he developed a program that has turned out hundreds of new field biologists who have gone onto careers in academia and public health.
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).
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.
The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti
15482A. E. Williams, I. Sanchez-Vargas, W. R. Reid, J. Y. Lin, A. W. E. Franz and K. E. Olson, Viruses, 12:18. 2020-12-15 14:45:29.
We used CRISPR/Cas9 to re-target a previously characterized locus (Chr2:321382225) and engineered mosquitoes expressing an inverted repeat (IR) dsRNA against the NS3/4A region of the ZIKV genome. Small RNA analysis revealed that the IR effector triggered the mosquito's siRNA antiviral pathway in bloodfed females. Nearly complete (90%) inhibition of ZIKV replication was found in vivo in both midguts and carcasses at 7 or 14 days post-infection (dpi). Furthermore, significantly fewer transgenic mosquitoes contained ZIKV in their salivary glands (p = 0.001), which led to a reduction in the number of ZIKV-containing saliva samples as measured by transmission assay. Our work shows that Ae. aegypti innate immunity can be co-opted to engineer mosquitoes resistant to ZIKV.
A patent review on strategies for biological control of mosquito vector
15377K. Parihar, M. Telang and A. Ovhal, World Journal of Microbiology and Biotechnology, 36:23. 2020-12-09 20:28:33.
This paper presents a comprehensive technology overview of patent documents disclosing biological agents for mosquito control. The patent analysis revealed that comparable number of patent documents were filed in two technology categories: non-recombinant agents and genetically modified (GM) agents. In the category of non-recombinant agents, toxic peptides from microbes and biological consortia seemed to be the earliest technology noted right from the year 1965 whereas the patent filings for suppression of mosquito population using genetic modification techniques have emerged from the year 2000 onwards. The United States of America is the leading patent filing jurisdiction followed by China and the Great Britain. Academic institutes have filed higher number of patent applications as compared to private companies. University of Florida was found to be the leading patent filing entity and its patents were focused on suppression of vector population using techniques such as release of insects with dominant lethal (RIDL) and RNA interference (RNAi).
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.
Advances in genetic engineering test democracy’s capacity for good decision-making
15027N. Kofler and R. Taitingfong, Boston Globe, 2020-11-09 15:31:50.
New advances in genetic engineering and their application for environmental conservation and public health are further testing our democracy’s capacity for good decision-making. With minimal public input, the Environmental Protection Agency recently approved the release of genetically modified mosquitoes in Florida and Texas. An application for the planting of GM American Chestnut trees, engineered to reproduce and spread in the wild, is currently under review by the US Department of Agriculture. And even more complex and powerful genetic technologies intended for environmental release are in the research pipeline.
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.
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
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).
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.
The future of beef might be a sausage fest
13479N. Johnson, grist, 2020-07-24 21:00:33.
N. Johnson. (2020) grist. A media report on the creation of a cow with a sex ratio altering genetic change expected to lead to 3/4 of the cow's offspring being males. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Meet Cosmo the Frankenbull: Scientists genetically engineer a bull calf so that 75 per cent of its offspring will be male
13476J. Pinkstone, Daily Mail, 2020-07-24 20:58:14.
J. Pinkstone (2020). Daily Mail. A media report on the creation of a cow with a sex ratio altering genetic change expected to lead to 3/4 of the cow's offspring being males. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Meet the first genetically modified bull. Why did scientists change it
13473J. Kessler, Free News, 2020-07-23 20:52:51.
J. Kessler (2020). Free News. UC Davis scientists have successfully introduced a bovine embryo, or the bovine SRY gene, which is responsible for the development of the male. This is the first demonstration of targeted gene insertion for large DNA sequences through embryo-mediated genome editing in cattle. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
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.
Field performance of sterile male mosquitoes released from an uncrewed aerial vehicle
12708J. Bouyer, N. J. Culbert, A. H. Dicko, M. G. Pacheco, J. Virginio, M. C. Pedrosa, L. Garziera, A. T. M. Pinto, A. Klaptocz, J. Germann, T. Wallner, G. Salvador-Herranz, R. A. Herrero, H. Yamada, F. Balestrino and M. J. B. Vreysen, Science Robotics, 5:10. 2020-06-15 20:48:48.
Genetic control methods of mosquito vectors of malaria, dengue, yellow fever, and Zika are becoming increasingly popular due to the limitations of other techniques such as the use of insecticides. The sterile insect technique is an effective genetic control method to manage insect populations. However, it is crucial to release sterile mosquitoes by air to ensure homogeneous coverage, especially in large areas. Here, we report a fully automated adult mosquito release system operated from an uncrewed aerial vehicle or drone. Our system, developed and tested in Brazil, enabled a homogeneous dispersal of sterile male Aedes aegypti while maintaining their quality, leading to a homogeneous sterile-to-wild male ratio due to their aggregation in the same sites. Our results indicate that the released sterile males were able to compete with the wild males in mating with the wild females; thus, the sterile males were able to induce sterility in the native female population. The use of drones to implement the sterile insect technique will lead to improvements in areal coverage and savings in operational costs due to the requirement of fewer release sites and field staff.
CRISPR/Cas9 gene drive technology to control transmission of vector-borne parasitic infections
12386M. Nateghi Rostami, Parasite Immunology, preprint:e12762. 2020-06-04 18:10:02.
Gene drive is the process of copying of an endonuclease-containing cassette that leads to increased frequency of inheritance of the desired traits in a targeted population. CRISPR/Cas9 technology is advancing genetic manipulation of insects in the field of gene drive experiments. The CRISPR/Cas9 drive could be engineered for genetic manipulation of parasites and/or vectors for disease control. A number of promising CRISPR/Cas9-based gene drive strategies that interfere with parasite development or impairs the reproductive capability of the insect vector, have been proposed in the laboratory for blocking transmission of malaria and leishmaniasis. Still several technical and ethical challenges remain to be addressed, none appear insuperable in this field.
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.
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.
Bioethical issues in genome editing by CRISPR-Cas9 technology
11216F. B. Ayanoglu, A. E. Elcin and Y. M. Elcin, Turkish Journal of Biology, 44:110-120. 2020-04-02 15:13:15.
Genome editing technologies have led to fundamental changes in genetic science. Among them, CRISPR-Cas9 technology particularly stands out due to its advantages such as easy handling, high accuracy, and low cost. It has made a quick introduction in fields related to humans, animals, and the environment, while raising difficult questions, applications, concerns, and bioethical issues to be discussed. Most concerns stem from the use of CRISPR-Cas9 to genetically alter human germline cells and embryos (called germline genome editing). Germline genome editing leads to serial bioethical issues, such as the occurrence of undesirable changes in the genome, from whom and how informed consent is obtained, and the breeding of the human species (eugenics). However, the bioethical issues that CRISPR-Cas9 technology could cause in the environment, agriculture and livestock should also not be forgotten. In order for CRISPR-Cas9 to be used safely in all areas and to solve potential issues, worldwide legislation should be prepared, taking into account the opinions of both life and social scientists, policy makers, and all other stakeholders of the sectors, and CRISPR-Cas9 applications should be implemented according to such legislations. However, these controls should not restrict scientific freedom. Here, various applications of CRISPR-Cas9 technology, especially in medicine and agriculture, are described and ethical issues related to genome editing using CRISPR-Cas9 technology are discussed. The social and bioethical concerns in relation to human beings, other organisms, and the environment are addressed.
Gene Drive – The Concept Explained
11402GeneConvene Global Collaborative, 2020-03-20 12:59:44.
This short video is intended to serve as a short tutorial that explains the general idea of 'drive' or 'gene drive' in the context of genetics. It provides the viewer with a basic understanding of the key genetic processes underlying the patterns of inheritance with which most people of familiar and explains how these processes are involved in gene drive. This video focuses on genetics and not applications of gene drive technologies and associated issues.
Autosomal suppression and fitness costs of an old driving X chromosome in Drosophila testacea
7363G. Keais, S. Lu and S. Perlman, Journal of Evolutionary Biology, 2020-01-28 21:58:18.
Driving X chromosomes (XDs) are meiotic drivers that bias their own transmission through males by killing Y-bearing gametes. These chromosomes can in theory spread rapidly in populations and cause extinction, but many are found as balanced polymorphisms or as ?cryptic? XDs shut down by drive suppressors. The relative likelihood of these outcomes, as well as the evolutionary pathways through which they come about, are not well-understood. An XD was recently discovered in the mycophagous fly, Drosophila testacea, presenting the opportunity to compare this XD with the well-studied XD of its sister species, Drosophila neotestacea. Comparing features of independently evolved XDs in young sister species is a promising avenue towards understanding how XDs and their counteracting forces change over time. In contrast to the XD of D. neotestacea, we find that the XD of D. testacea is old, with its origin predating the radiation of three species: D. testacea, D. neotestacea, and their shared sister species, Drosophila orientacea. Motivated by the suggestion that older XDs should be more deleterious to carriers, we assessed the effect of the XD on both male and female fertility. Unlike what is known from D. neotestacea, we found a strong fitness cost in females homozygous for the XD in D. testacea: a large proportion of homozygous females failed to produce offspring after being housed with males for several days. Our male fertility experiments show that while XD male fertility is lower under sperm depleting conditions, XD males have comparable fertility to males carrying a standard X chromosome under a free mating regime, which may better approximate conditions in wild populations of D. testacea. Lastly, we demonstrate the presence of autosomal suppression of X chromosome drive. Our results provide support for a model of XD evolution where the dynamics of young XDs are governed by fitness consequences in males, whereas in older XD systems, both suppression and fitness consequences in females likely supersede male fitness costs.
Metaphor, Trust and Support for Non-native Species Control
13833P. A. Kohl, S. J. Collins and M. Eichholz, Environmental Communication, 14:672-685. 2020-01-07 15:29:47.
This experimental study used a representative sample of U.S. residents (N = 1,042) to test whether the use of the term "invasive" increases support for non-native species control efforts. The term invasive had a small influence on support for two out of three non-native species control methods. We also found stronger support for control methods using gene editing technologies than control methods using poison.
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.
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.
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.
Effects of a male meiotic driver on male and female transcriptomes in the house mouse
6639A. Lindholm, A. Sutter, S. Kunzel, D. Tautz and H. Rehrauer, Proceedings of the Royal Society B-Biological Sciences, 286:1-8. 2019-11-13 20:18:05.
Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of the t haplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus, much of the activity of the t haplotype occurs in trans, and as upregulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.
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.
Gene Drives: Dynamics and Regulatory Matters-A Report from the Workshop “Evaluation of Spatial and Temporal Control of Gene Drives,” April 4-5, 2019, Vienna
12396B. Giese, J. L. Friess, N. H. Barton, P. W. Messer, F. Debarre, M. F. Schetelig, N. Windbichler, H. Meimberg and C. Boete, Bioessays, 41:3. 2019-10-07 18:26:19.
Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.
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.
Synthetic Biology: Research Needs for Assessing Environmental Impacts
17467C. M. Warner, S. R. Carter, R. F. Lance, F. H. Crocker, H. N. Meeks, B. L. Adams, M. L. Magnuson, T. Rycroft, K. Pokrzywinski and E. J. Perkins, Synthetic Biology 2020: Frontiers in Risk Analysis and Governance, 2019-08-01 18:23:43.
Synthetic biology and its applications have the potential to greatly improve economic development, public health, environmental stewardship, technological advancement, and many other areas. In May 2017, sixty individuals gathered in Lexington, Massachusetts for a workshop sponsored by the U.S. Army Engineer Research and Development Center (ERDC) to discuss applications of synthetic biology with likely or intended interaction with the environment. Representatives from academia, government agencies, industry, and non-governmental organizations convened to identify knowledge gaps and research needs to assess potential environmental impacts from these technologies. The group discussed challenges in environmental risk assessment, regulation, and community engagement for emerging synthetic biology technologies. The workshop was structured around four hypothetical case studies, including the use of gene drive engineered organisms to control infectious disease vectors, engineered microbes for bioremediation, cell-free applications for advanced chemical production, and engineered viruses for water treatment. Meeting these research needs will facilitate appropriate environmental risk assessment and informed decision making for the development and potential deployment of synthetic biology organisms and components in the environment.
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.
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.
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
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.
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.
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.
The EU regulatory framework on genetically modified organisms (GMOs)
3893Bruetschy, C, Transgenic Research, 28:169-174. 2019-01-11 00:00:00.
The European Union (EU) legislation on genetically modified organisms (GMOs) aims to ensure a high level of protection for human, animal and environmental health and a well-functioning EU internal market. The framework regulates the release of GMOs into the environment and their use as, or in, food and feed. It has three main pillars: pre-market authorisation based on a prior risk assessment, traceability and labelling. Within this legal framework, the EU has authorised the placing on the market of 118 GMOs so far. These have been obtained through long-standing techniques of genetic modification, namely transgenesis. Following the adoption of the GMO legislation, new techniques of genetic modification, including new mutagenesis techniques, have been developed, which have raised questions regarding the applicability of the GMO legislation and attracted a lot of attention from stakeholders and the general public. This article provides an overview of EU GMO legislation and implementation of the EU Court of Justice ruling on organisms obtained by mutagenesis techniques, issued in July 2018. It also updates on the recent initiatives by the European Commission and EU Member States on new developments in biotechnology. The manuscript is based on the author's contribution at the OECD Conference on Genome Editing, Applications in Agriculture, Implications for Health, Environment and Regulation held in Paris on 28-29 June 2018. It is complemented with updated information.
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.
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 driving the farm: who decides, who owns, and who benefits?
3907Montenegro de Wit, M, Agroecology and Sustainable Food Systems, 43:1054-1074. 2019-01-05 00:00:00.
This commentary essay explores the social and ecological implications of gene-driving agriculture.
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.
Ecological effects on underdominance threshold drives for vector control
16267D. Khamis, C. El Mouden, K. Kura and M. B. Bonsall, Journal of Theoretical Biology, 456:1-15. 2018-11-07 16:39:27.
Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair of chromosomes at the same locus or homozygously on different pairs at different loci, genetic lethality that affects both sexes or only females, and bi-sex or male-only releases.
Why is this African village letting mosquitoes in?
4711BBC, BBC, 2018-10-19 00:00:00.
This is a BBC spot about the first release of genetically modified mosquitoes in Africa by the Target Malaria team. Very little information about gene drive but the context of this spot is notable.
A swarm of mutant mosquitoes is out to eradicate malaria
4575O'Mahony, J, Wired, 2018-09-21 00:00:00.
Over the next year in the village of Bana, Burkina Faso, a group of scientists will set loose up to 10,000 mosquitoes sprinkled with fluorescent dust. The sterile, male swarm will represent the first ever release of a genetically modified, malaria carrying mosquito species into the wild. It's a milestone not only for science, but also for community engagement and regulatory hurdles in Africa.; ; Most significantly, however, these mosquitoes will lay the ground for the eventual deployment of a powerful biological tool which researchers hope will one day stop malaria altogether.
Gene Drive
4551Collins, CH, Scientific American, 2018-09-14 00:00:00.
Research into a genetic engineering technology that can permanently change the traits of a population or even an entire species is progressing rapidly. The approach uses gene drives—genetic elements that pass from parents to unusually high numbers of their offspring, thereby spreading through populations rather quickly. Gene drives occur naturally but can also be engineered, and doing so could be a boon to humanity in many ways. The technology has the potential to stop insects from transmitting malaria and other terrible infections, enhance crop yields by altering pests that attack plants, render corals resistant to environmental stress, and keep invasive plants and animals from destroying ecosystems. Yet investigators are deeply aware that altering or even eliminating a species could have profound consequences. In response, they are developing rules to govern the transfer of gene drives from the laboratory into future field tests and wider use.
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.
When Evolution Fights Back Against Genetic Engineering
4548Borel, B, Quanta Magazine, 2018-09-08 00:00:00.
In a crowded auditorium at New York’s Cold Spring Harbor Laboratory in August, Philipp Messer, a population geneticist at Cornell University, took the stage to discuss a powerful and controversial new application for genetic engineering: gene drives.; ; Gene drives can force a trait through a population, defying the usual rules of inheritance. A specific trait ordinarily has a 50-50 chance of being passed along to the next generation. A gene drive could push that rate to nearly 100 percent. The genetic dominance would then continue in all future generations. You want all the fruit flies in your lab to have light eyes? Engineer a drive for eye color, and soon enough, the fruit flies’ offspring will have light eyes, as will their offspring, and so on for all future generations. Gene drives may work in any species that reproduces sexually, and they have the potential to revolutionize disease control, agriculture, conservation and more. Scientists might be able to stop mosquitoes from spreading malaria, for example, or eradicate an invasive species.
Gene drives accelerate evolution – but we need brakes
4590Tsai, Y-HP, Tony, The Conversation, 2018-07-05 00:00:00.
Worried about mice in the kitchen? Fed up with pigeons on your way to work? Teed off by weeds on your lawn? Recent work points to a way that might just reduce – or even eliminate – unwanted species in a short period. The method is based on something called a gene drive – a method of making changes to an entire population of a specific species by altering its genetic material (its genome).; ; Although gene drives are today restricted to the confines of a few laboratories, they have immense promise. In addition to potential pest removal they might, for example, allow us to make livestock more resilient to disease, enhance the nutritional value of crops, or eliminate the mosquitoes that transmit infectious diseases such as zika and malaria.
How science could wipe out disease-carrying mosquitoes and save lives
4553Elliot, JK, Global News, 2018-06-15 00:00:00.
Mosquitoes kill hundreds of thousands of people every year by spreading disease in tropical areas. They’re also the worst part of many cottage weekends and camping trips in North America.; ; But it doesn’t have to be that way.; ; Scientists are developing two methods for eliminating mosquitoes that carry disease, which could be deployed sometime within the next 15 years.; ; The first, dubbed the sterile insect technique, could be used to kill off disease-carrying mosquitoes in urban areas.
Gene drive put to work for first time.
4542Arnason, R, The Western Producer, 2018-05-03 00:00:00.
A disruptive technology that potentially could eliminate or reduce the need for insecticides may soon be coming to market. In a paper published April 17 in the Proceedings of the National Academy of Sciences, University of California, San Diego biologists announced they have developed a gene drive to control an agricultural pest. The pest is the spotted wing drosophila, a fruit fly that damages berry and fruit crops. “This is the first gene drive system in a major worldwide crop pest,” said Omar Akbari, of UC San Diego. “This system could in the future be used to control populations of (drosophila).” A gene drive is a tool to spread a genetic alteration into a wild population of a certain species. In nature, there is on average a 50 percent chance of a parent passing a particular trait to an offspring. With a gene drive, a specified gene is inherited by all offspring, even if it is present in only one parent
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.
Gene Drives – Wundermittel? Biowaffe?
12380Swiss Academy of Sciences, 2018-02-19 21:02:40.
Gene drives are genetic elements that skew the pattern of inheritance of a given characteristic in sexually reproduc- ing 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.
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.
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.
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.
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.
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.
Transmission and drive involving parasitic B chromosomes
3984Jones, RN, Genes, 9:e388. 2018-01-02 00:00:00.
B chromosomes (Bs) are enigmatic additional elements in the genomes of thousands of species of plants, animals, and fungi. How do these non-essential, harmful, and parasitic chromosomes maintain their presence in their hosts, making demands on all the essential functions of their host genomes? The answer seems to be that they have mechanisms of drive which enable them to enhance their transmission rates by various processes of non-mendelian inheritance. It is also becoming increasingly clear that the host genomes are developing their own mechanisms to resist the impact of the harmful effects of the Bs.
Rats join mosquitoes as targets for ‘gene drive’ pest control.
4596Hirschler, B, Reuters, 2017-12-17 00:00:00.
Rodents have joined mosquitoes in the cross-hairs of scientists working on a next-generation genetic technology known as “gene drive” to control pests.; Researchers in Scotland said on Tuesday they had developed two different ways to disrupt female fertility in rats and mice, building on a similar approach that has already been tested in the lab to eliminate malaria-carrying mosquitoes.; So-called gene drives push engineered genes through multiple generations by over-riding normal biological processes, so that all offspring carry two copies. Usually, animals would receive one copy of a gene from the mother and one from the father.
Open, Local, and Obligated
5467Yale University, 2017-12-13 17:04:29.
Kevin Esvelt, PhD, assistant professor at the MIT Media Lab and leader of the Sculpting Evolution Group talks about the need for new scientific structures based on transparency and open. This lecture was given at the 2017 Editing Nature Summit.
‘Gene Drives’ Are Too Risky for Field Trials, Scientists Say
4600Zimmer, C, New York Times, 2017-11-16 00:00:00.
In 2013, scientists discovered a new way to precisely edit genes — technology called Crispr that raised all sorts of enticing possibilities. Scientists wondered if it might be used to fix hereditary diseases, for example, or to develop new crops.; ; One of the more intriguing ideas came from Kevin M. Esvelt and his colleagues at Harvard University: Crispr, they suggested, could be used to save endangered wildlife from extinction by implanting a fertility-reducing gene in invasive animals — a so-called gene drive.
How Genetically Modified Mice Could One Day Save Island Birds
4593Borel, B, Audubon, 2017-06-07 00:00:00.
The silent black-and-white footage opens on a seemingly tranquil setting: a burrow where an Atlantic Petrel tends to its chick. Then mice begin scurrying in and out of frame. The dark blurs jostle the adult, darting up to the exposed chick and tearing off bloody bites. They’re eating it alive.; ; The horrific scene is captured by nest cams on Gough (rhymes with “off”), a rugged volcanic island about 1,700 miles west of South Africa. It has one of the world’s largest seabird nesting colonies, with millions of birds representing 22 species. It’s also home to hundreds of thousands of mice, descendants of stowaways on 19th-century seal-hunting ships. The tiny predators devour some 900,000 chicks a year and threaten to decimate the island’s Atlantic Petrels and Tristan Albatrosses, which breed here almost exclusively. In a rodent-free landscape, more than two-thirds of the albatross chicks should make it to adulthood; on Gough, mice cut survival to as low as 10 percent.
Illustrated experiment: modifying mosquitoes to save millions of lives
4599Volpicelli, G, Wired, 2017-03-26 00:00:00.
Malaria, a disease transmitted by a type of mosquito called Anopheles, kills 500,000 people every year, most of them in Africa. But Andrea Crisanti, professor of molecular parasitology at London's Imperial College, has a plan to eradicate it in many countries.
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.
Gene drives do not always increase in frequency: from genetic models to risk assessment
4036de Jong, TJ, Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety, 12:299-307. 2017-01-14 00:00:00.
Homing genes encode endonucleases that make a double stranded break in the DNA, destroying a target site on the homologous chromosome. When the cell repairs the break the homing allele is copied, converting a heterozygote into a homozygote. This results in gene drive (GD), an overrepresentation of the homing allele in the next generation. GD may propel CRISPR-Cas9 genes and new genes physically coupled to the GD through natural populations. I revisit the population genetic models of GD with the aim of making these models more understandable to non-specialists. What can we learn about risk evaluation from the models? A GD with no or a small effect on fitness (viability) always spreads in the population and goes to fixation. That is provided that no resistance mechanism evolves, for instance due to a mutation in the target site. However, when GDs have a large negative effect on fitness, their spread depends on a threshold or they may not spread at all. The chance of GDs increasing until fixation is much higher in systems with meiotic drive than in systems with embryo conversion. The presence or absence of a meiotic promoter is therefore relevant to take into account in the environmental risk assessment.
Sperm competition suppresses gene drive among experimentally evolving populations of house mice
4056Manser, AL, A. K.; Simmons, L. W.; Firman, R. C., Molecular Ecology, 26:5784-5792. 2017-01-14 00:00:00.
Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well-known drive gene called t haplotype post hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations. Previous work on these selection lines reported an increase in sperm competitive ability in males evolving under polyandry. Here, we show that this evolutionary response can be partly attributed to gene drive. We demonstrate that drive-carrying males are substantially compromised in their sperm competitive ability. As a consequence, we found that t frequencies declined significantly in the polyandrous lines while remaining at stable, high levels in the monandrous lines. For the first time in a vertebrate, we thus provide direct experimental evidence that the mating system of a species can have important repercussions on the spread of drive genes over evolutionary relevant timescales. Moreover, our work highlights how the covert action of drive genes can have major, potentially unintended impact on our study systems.
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.
A large gene family in fission yeast encodes spore killers that subvert Mendel’s law
4049Hu, WJ, Z. D.; Suo, F.; Zheng, J. X.; He, W. Z.; Du, L. L., eLife, 6:e28567. 2017-01-07 00:00:00.
Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve.
Using Gene Drive to Control Malaria
4718The Scientist, The Scientist, 2016-12-31 00:00:00.
This article provides illustrations for how gene drive works, how gene drives spread, and how gene drive could be used to control malaria using population-wide gene knockout, skewed sex ratio, and population-wide gene knock-in techniques. Visit the article to view all illustrations.
National Academies hit the brakes on gene drive-modified organisms
5657Abbasi, J., JAMA-Journal of the American Medical Association, 316:482-483. 2016-12-17 18:11:25.
Despite their potential for fighting Zika, malaria, and other public health scourges, organisms that have been engineered to quickly spread genetic modifications through a population—and possibly an entire species—are not ready for release into the wild, a committee of interdisciplinary experts concluded in a recent report by the National Academies of Sciences, Engineering, and Medicine (http://bit.ly/1UHuqQk). So-called gene drive–modified organisms “require more research in laboratories and highly controlled field trials,” the committee said in a statement (http://bit.ly/1tkWCTO). Gene drives are systems of “biased inheritance” that enhance a genetic element’s ability to pass from parent organism to offspring through sexual reproduction. These selfish genetic elements could be genes or their fragments, all or parts of chromosomes, or noncoding DNA, the report stated.
Gene drives: The good, the bad, and the hype
4604Ouagrham-Gormley, SBV, Kathleen M., The Bulletin of the Atomic Scientists, 2016-10-14 00:00:00.
Since the early 2000s, many advances in the life sciences, such as the artificial synthesis of the poliovirus and the gain-of-function experiments that enhanced the transmissibility of the H5N1 flu virus, have led to warnings that bioweapons development would soon be getting easier, cheaper, and faster for states and non-state actors alike. The new gene-editing technique known as Crispr has raised similar concerns because it allows researchers to edit genomes precisely, quickly, and cheaply. It has also facilitated the development of “gene drives,” which in theory allow scientists to permanently introduce a genetic alteration into an entire animal or plant population. Gene drives are being investigated as tools to eradicate infectious diseases or control pests that cause agricultural, economic, and environmental damages; yet they have also raised concerns. The absence of clear safety guidelines, coupled with ambiguous government regulations, has nurtured fears of an accidental or voluntary release of a gene drive in nature that could cause irreparable damage. On the security front, the presumed simplicity and accessibility of Crispr raise the possibility that states, terrorists, or rogue scientists might use the technology to modify genomes to develop malicious gene drives and create novel bioweapons that could spread more quickly, cheaply, and globally than traditional bioweapons agents.
Genetic Engineering and Diseases – Gene Drive & Malaria
4714Kurzgesagt – In a Nutshell, 2016-09-21 00:00:00.
This video focuses on the basic applications of gene drive to malaria eradication and leave the viewer with the question “what do you think?”
Extinctions to order: Gene-ocide.
4606The Economist, The Economist, 2016-09-17 00:00:00.
IN A competition to find the world’s least-loved animal, the mosquito would be hard to beat. Only a few species of the insect carry the parasites that cause human diseases such as West Nile virus, dengue and yellow fever, but the harm they cause is enormous. Malaria kills more than 400,000 people, mostly children, every year. Zika has spread to dozens of countries (see article). If species such as Anopheles gambiae and Aedes aegypti could be eradicated, the world would surely be a better place.; ; Genetic engineers have already taken some steps in that direction: male A. aegypti mosquitoes that have been modified to become sterile have been released in Brazil, for example. Such approaches, controversial though they are among some greens, are limited in their impact and geographical range. A nascent technique called a “gene drive”, which could make it far easier to wipe out species, raises harder questions.
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”.
Re-Coding for Conservation
4603Hawkes, A, Bay Nature Magazine, 2016-06-27 00:00:00.
very year, as summer turns to fall, the mouse population on the South Farallon Islands explodes to plague-like densities, numbering 490 mice per acre, among the highest found on any island in the world. The scientists who live and work there describe the assault of the invasive house mouse as a kind of purgatory in the otherwise stunning, windswept smattering of rocky islets and sea stacks 30 miles outside the Golden Gate. “At night they would be everywhere,” says Peter Pyle, a wildlife biologist who spent more than 20 fall seasons living at the research station on Southeast Farallon Island. “I had them crawling on top of me at night and in my hair. I tried to mouse-proof the house but we’d catch 50 mice in the night.”
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.
When Extinction Is a Humanitarian Cause
4601Adelman, Z, MIT Technology Review, 2016-02-12 00:00:00.
Humans have driven species to extinction through our hunger, our ignorance, our desire for economic growth, and our indifference. Will one species of mosquito be the first we eliminate for humanitarian ; The mosquito is Aedes aegypti. It is commonly known as the yellow fever mosquito and, in more recent years, has become known as the dengue mosquito for spreading a hemorrhagic disease that disproportionately affects small children and has high public health costs. Now it's the Zika mosquito, suspected of transmitting Zika virus with a potential association to microcephaly in newborns.
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.
Intragenomic conflict produces sex ratio dynamics that favor maternal sex ratio distorters
4099Rood, ESF, S., Ecology and Evolution, 6:8085-8093. 2016-01-17 00:00:00.
Maternal sex ratio distorters (MSDs) are selfish elements that enhance their transmission by biasing their host's sex allocation in favor of females. While previous models have predicted that the female-biased populations resulting from sex ratio distortion can benefit from enhanced productivity, these models neglect Fisherian selection for nuclear suppressors, an unrealistic assumption in most systems. We used individual-based computer simulation modeling to explore the intragenomic conflict between sex ratio distorters and their suppressors and explored the impacts of these dynamics on population-level competition between species characterized by MSDs and those lacking them. The conflict between distorters and suppressors was capable of producing large cyclical fluctuations in the population sex ratio and reproductive rate. Despite fitness costs associated with the distorters and suppressors, MSD populations often exhibited enhanced productivity and outcompeted non-MSD populations in single and multiple-population competition simulations. Notably, the conflict itself is beneficial to the success of populations, as sex ratio oscillations limit the competitive deficits associated with prolonged periods of male rarity. Although intragenomic conflict has been historically viewed as deleterious to populations, our results suggest that distorter-suppressor conflict can provide population-level advantages, potentially helping to explain the persistence of sex ratio distorters in a range of taxa.
A meiotic drive element in the maize pathogen Fusarium verticillioides is located within a 102 kb region of chromosome V
4098Pyle, JP, T.; Merrill, B.; Nsokoshi, C.; McCall, M.; Proctor, R. H.; Brown, D. W.; Hammond, T. M., G3-Genes Genomes Genetics, 6:2543-2552. 2016-01-16 00:00:00.
Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (Sk(K)) that causes nearly all surviving meiotic progeny from an Sk(K) x Spore killer-susceptible (Sk(S)) cross to inherit the Sk(K) allele. Sk(K) has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an Sk(K) x Sk(S) mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of Sk(K) to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to Sk(S) genotypes, Sk(K) genotypes have one extra gene within this region for a total of 42 genes. The additional gene in Sk(K) genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hyper-variable regions, the longest of which includes SKC1. The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed.
R2d2 drives selfish sweeps in the house mouse
4084Didion, JPM, A. P.; Yadgary, L.; Bell, T. A.; McMullan, R. C.; de Solorzano, L. O.; Britton-Davidian, J.; Bult, C. J.; Campbell, K. J.; Castiglia, R.; Ching, Y. H.; Chunco, A. J.; Crowley, J. J.; Chesler, E. J.; Forster, D. W.; French, J. E.; Gabriel, S. I.; Gatti, D. M.; Garland, T.; Giagia-Athanasopoulou, E. B.; Gimenez, M. D.; Grize, S. A.; Gunduz, I.; Holmes, A.; Hauffe, H. C.; Herman, J. S.; Holt, J. M.; Hua, K. J.; Jolley, W. J.; Lindholm, A. K.; Lopez-Fuster, M. J.; Mitsainas, G.; Mathias, M. D.; McMillan, L.; Ramalhinho, M. D. M.; Rehermann, B.; Rosshart, S. P.; Searle, J. B.; Shiao, M. S.; Solano, E.; Svenson, K. L.; Thomas-Laemont, P.; Threadgill, D. W.; Ventura, J.; Weinstock, G. M.; Pomp, D.; Churchill, G. A.; de Villena, F. P. M., Molecular Biology and Evolution, 33:1381-1395. 2016-01-02 00:00:00.
A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding inmultiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
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.)
Playing God with mosquitoes? We humans have loftier aims.
4608Pugh, J, The Conversation, 2015-12-02 00:00:00.
In a startling development in “gene-drive” technology, a team of researchers at the University of California has succeeded in creating genetically modified mosquitoes incapable of spreading the malaria parasite to humans, and which could potentially spread this trait rapidly throughout mosquito populations in the wild.; ; This success has the potential to be translated into a huge global health benefit. Although global malarial deaths have been in decline over the past decade or so, the WHO estimates that malaria has been responsible for over 400,000 deaths this year alone.
What’s a Gene Drive? And what are the risks and benefits?
4712Risk Bites, Arizona State University, 2015-11-30 00:00:00.
This video uses ‘white board cartooning’ as a means of illustrating concepts.
What is Gene Drive?
4717Entomological Society of America, 2015-07-01 00:00:00.
A fact sheet from the Entomological Society of America.
The next generation of rodent eradications: Innovative technologies and tools to improve species specificity and increase their feasibility on islands
4109Campbell, KJB, J.; Eason, C. T.; Glen, A. S.; Godwin, J.; Gould, F.; Holmes, N. D.; Howald, G. R.; Madden, F. M.; Ponder, J. B.; Threadgill, D. W.; Wegmann, A. S.; Baxter, G. S., Biological Conservation, 185:47-58. 2015-01-07 00:00:00.
Rodents remain one of the most widespread and damaging invasive alien species on islands globally. The current toolbox for insular rodent eradications is reliant on the application of sufficient anticoagulant toxicant into every potential rodent territory across an island. Despite significant advances in the use of these toxicants over recent decades, numerous situations remain where eradication is challenging or not yet feasible. These include islands with significant human populations, unreceptive stakeholder communities, co-occurrence of livestock and domestic animals, or vulnerability of native species. Developments in diverse branches of science, particularly the medical, pharmaceutical, invertebrate pest control, social science, technology and defense fields offer potential insights into the next generation of tools to eradicate rodents from islands. Horizon scanning is a structured process whereby current problems are assessed against potential future solutions. We undertook such an exercise to identify the most promising technologies, techniques and approaches that might be applied to rodent eradications from islands. We highlight a Rattus-specific toxicant, RNA interference as species-specific toxicants, rodenticide research, crab deterrent in baits, prophylactic treatment for protection of non-target species, transgenic rodents, virus vectored immunocontraception, drones, self-resetting traps and toxicant applicators, detection probability models and improved stakeholder community engagement methods. We present a brief description of each method, and discuss its application to rodent eradication on islands, knowledge gaps, challenges, whether it is incremental or transformative in nature and provide a potential time-line for availability. We outline how a combination of new tools may render previously intractable rodent eradication problems feasible. (C) 2014 Elsevier Ltd. All rights reserved.
Confinement of gene drive systems to local populations: A comparative analysis
4192Marshall, JMH, B. A., Journal of Theoretical Biology, 294:153-171. 2012-01-10 00:00:00.
Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered synthetic drive systems have provided encouragement for this strategy; but at the same time have been greeted with caution over the concern that transgenes may spread into countries and communities without: their consent. Consequently, there is also interest in gene drive systems that, while strong enough to bring about local population replacement, are unable to establish themselves beyond a partially isolated release site, at least during the testing phase. Here, we develop simple deterministic and stochastic models to compare the confinement properties of a variety of gene drive systems. Our results highlight several systems with desirable features for confinement-a high migration rate required to become established in neighboring populations, and low-frequency persistence in neighboring populations for moderate migration rates. Single-allele underdominance and single-locus engineered underdominance have the strongest confinement properties, but are difficult to engineer and require a high introduction frequency, respectively. Toxin-antidote systems such as Semele. Merea and two-locus engineered underdominance show promising confinement properties and require lower introduction frequencies. Killer-rescue is self-limiting in time, but is able to disperse to significant levels in neighboring populations. We discuss the significance of these results in the context of a phased release of transgenic mosquitoes, and the need for characterization of local ecology prior to a release. (C) 2011 Elsevier Ltd. All rights reserved.
Problem formulation in the environmental risk assessment for genetically modified plants
4219Wolt, JDK, Paul; Raybould, Alan; Fitzpatrick, Julie W.; Burachik, Moisés; Gray, Alan; Olin, Stephen S.; Schiemann, Joachim; Sears, Mark; Wu, Felicia, Transgenic Research, 19:425-436. 2010-01-17 00:00:00.
Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation.
Evolution of the Schlafen genes, a gene family associated with embryonic lethality, meiotic drive, immune processes and orthopoxvirus virulence
4221Bustos, ON, S.; Ayers, G.; Casola, C.; Perez-Lamigueiro, M. A.; Chippindale, P. T.; Pritham, E. J.; de la Casa-Esperon, E., Gene, 447:11-Jan. 2009-01-19 00:00:00.
Genes of the Schlafen family, first discovered in mouse, are expressed in hematopoietic cells and are involved in immune processes. Previous results showed that they are candidate genes for two major phenomena: meiotic drive and embryonic lethality (DDK syndrome). However, these genes remain poorly understood, mostly due to the limitations imposed by their similarity, close location and the potential functional redundancy of the gene family members. Here we use genomic and phylogenetic studies to investigate the evolution and role of this family of genes. Our results show that the Schlafen family is widely distributed in mammals, where we recognize four major clades that experienced lineage-specific expansions or contractions in various orders, including primates and rodents. In addition, we identified members of the Schlafen family in Chondrichthyes and Amphibia, indicating an ancient origin of these genes. We find evidence that positive selection has acted on many Schlafen genes. Moreover, our analyses indicate that a member of the Schlafen family was horizontally transferred from murine rodents to orthopoxviruses, where it is hypothesized to play a role in allowing the virus to survive host immune defense mechanisms. The functional relevance of the viral Schlafen sequences is further underscored by our finding that they are evolving under purifying selection. This is of particular importance, since orthopoxviruses infect mammals and include variola, the causative agent of smallpox, and monkeypox, an emerging virus of great concern for human health. (C) 2009 Elsevier B.V. All rights reserved.
The distribution of B chromosomes across species
4297Palestis, BGT, R.; Burt, A.; Jones, R. N., Cytogenetic and Genome Research, 106:151-158. 2004-01-15 00:00:00.
In this review we look at the broad picture of how B chromosomes are distributed across a wide range of species. We review recent studies of the factors associated with the presence of Bs across species, and provide new analyses with updated data and additional variables. The major obstacle facing comparative studies of B chromosome distribution is variation among species in the intensity of cytogenetic study. Because Bs are, by definition, not present in all individuals of a species, they may often be overlooked in species that are rarely studied. We give examples of corrections for differences in study effort, and show that after a variety of such corrections, strong correlations remain. Several major biological factors are associated with the presence of B chromosomes. Among flowering plants, Bs are more likely to occur in outcrossing than in inbred species, and their presence is also positively correlated with genome size and negatively with chromosome number. They are no more frequent in polyploids than in diploids, nor in species with multiple ploidies. Among mammals, Bs are more likely to occur in species with karyotypes consisting of mostly acrocentric chromosomes. We find no evidence for an association with chromosome number or genome size in mammals, although the sample for genome size is small. The associations with breeding system and acrocentric chromosomes were both predicted in advance, but those with genome size and chromosome number were discovered empirically and we can offer only tentative explanations for the very strong associations we have uncovered. Our understanding of why B chromosomes are present in some species and absent in others is still in its infancy, and we suggest several potential avenues for future research. Copyright (C) 2004 S. Karger AG, Basel.
Inverted meiosis and meiotic drive in mealybugs
4285Bongiorni, SF, P.; Pippoletti, D.; Prantera, G., Chromosoma, 112:331-341. 2004-01-03 00:00:00.
In the males of lecanoid coccids, or mealybugs, an entire, paternally derived, haploid chromosome set becomes heterochromatic after the seventh embryonic mitotic cycle. In females, both haploid sets are euchromatic throughout the life cycle. In mealybugs, as in all homopteran species, chromosomes are holocentric. Holocentric chromosomes are characterized by the lack of a localized centromere and consequently of a localized kinetic activity. In monocentric species, sister chromatid cohesion and monopolar attachment play a pivotal role in regulating chromosome behavior during the two meiotic divisions. Both these processes rely upon the presence of a single, localized centromere and as such cannot be properly executed by holocentric chromosomes. Here we furnish further evidence that meiosis is inverted in both sexes of mealybugs and we suggest how this might represent an adaptation to chromosome holocentrism. Moreover, we reveal that at the second meiotic division in males a monopolar spindle is formed, to which only euchromatic chromosomes become attached. By this mechanism the paternally derived, heterochromatic, haploid chromosome set strictly segregates from the euchromatic one, and it is then excluded from the genetic continuum as a result of meiotic drive.
Nonrandom segregation during meiosis: the unfairness of females
4328de Villena, FPMS, C., Mammalian Genome, 12:331-339. 2001-01-06 00:00:00.
Most geneticists assume that chromosome segregation during meiosis is Mendelian (i.e., each allele at each locus is represented equally in the gametes). The great majority of reports that discuss non-Mendelian transmission have focused on systems of gametic selection, such as the mouse t-haplotype and Segregation distorter in Drosophila, or on systems in which post-fertilization selection takes place, Because the segregation of chromosomes in such systems is Mendelian and unequal representation of alleles among offspring is achieved through gamete dysfunction or embryonic death, there is a common perception that true disturbances in the randomness of chromosome segregation are rare and of limited biological significance. In this review we summarize data on nonrandom segregation in a wide variety of genetic systems. Despite apparent differences between some systems, the basic requirements for nonrandom segregation can be deduced from their shared characteristics: i) asymmetrical meiotic division(s); ii) functional asymmetry of the meiotic spindle poles: and iii) functional heterozygosity at a locus that mediates attachment of a chromosome to the spindle. The frequency with which all three of these requirements al e fulfilled in natural populations is an known, but our analyses indicate that nonrandom segregation occurs with sufficient frequency during female meiosis, and in exceptional cases of male meiosis, that it has important biological, clinical, and evolutionary consequences.
Transmission ratio distortion due to the bl gene in table beet
4327Austin, DG, I. L., Journal of the American Society for Horticultural Science, 126:340-343. 2001-01-05 00:00:00.
The bl gene conditions a blotchy phenotype (irregular sectors of red and white root color) in table beet (Beta vulgaris ssp, vulgaris). Segregation of the bl gene was found to be consistent with a single recessive gene, however, some evidence for a departure from a single gene model was observed when blbl plants were used as females. Tn this report, segregation of the bl gene was examined in greater detail in 10 F-2 populations derived from crosses of red blotchy-rooted females (genotype blbl, denoted blotchy) with red-rooted males (BlBl, denoted red,), and 10 Fz populations derived from the reciprocal cross. Tn blbl x BlBl crosses, the proportion of red-rooted progeny was greater than 0.75 in seven of the crosses, and was significantly greater (P = 0.005) in three crosses. A test for heterogeneity was significant, indicating that the proportion of red-rooted progeny differed significantly in these 10 crosses. In BlBl x blbl crosses, the proportion of red-rooted progeny was <0.75 in seven of the crosses and there were no significant departures from the expected 3:1 ratio in any of the individual crosses. However, a pooled estimate of the segregation ratio showed a significant (P < 0.01) departure from the 3:1 ratio (pooled estimate = 0.71.), These data demonstrate transmission ratio distortion at the bl locus when blbl plants are used as both females and males in matings with wild type plants, but the degree of distortion is greater when blbl plants are used as females. Ratio distortion in such crosses may be due to a variety of factors, including increased transmission of the bl gene through female or male gametes depending on the direction of the cross, reduced fitness of maternally derived blbl progeny, epigenetic phenomena, increased fitness of paternally derived blbl progeny, or linkage of the bl gene to viability genes.
Invasion of one insect species, Adalia bipunctata, by two different male-killing bacteria
4355Hurst, GDDvdS, J. H. G.; Majerus, T. M. O.; Bertrand, D.; Zakharov, I. A.; Baungaard, J.; Volkl, W.; Stouthamer, R.; Majerus, M. E. N., Insect Molecular Biology, 8:133-139. 1999-01-13 00:00:00.
Male-killing bacteria, which are inherited through the female line and kill male progeny only, are known from five different orders of insect. Our knowledge of the incidence of these elements has stemmed from discovery of their phenotype in different species, Our estimate of the frequency with which insects have been invaded by these elements therefore depends on each observation of the male-killing phenotype within a species being associated with a single microorganism. We here record an example of a single insect species being infected with two taxonomically distinct male-killing bacteria. Western European populations of the two-spot ladybird, Adalia bipunctata, have previously been shown to bear a male-killing Rickettsia, However, we here show that the majority of the male-killing lines tested from Central and Eastern Europe do not bear this bacterium. Rather, 16S rDNA sequence analysis suggests male-killing is associated with st member of the genus Spiroplasma. We discuss this conclusion in relation to the evolutionary genetics of male-killing bacteria, and the evolution of male-killing behaviour in the eubacteria.
Transmission ratio distortion at the INS-IGF2 VNTR
4352Eaves, IAB, S. T.; Forster, P.; Ferber, K. M.; Ehrmann, D.; Wilson, A. J.; Bhattacharyya, S.; Ziegler, A. G.; Brinkmann, B.; Todd, J. A., Nature Genetics, 22:324-325. 1999-01-10 00:00:00.
Transmission ratio distortion (TRD) is defined as a statistically significant departure from mendelian transmission. So far, evidence of this in humans has been limited or controversial1,2,3,4, and the few established examples involve chromosome rearrangements in lower organisms5.; ; The variable number of tandem repeat (VNTR) polymorphism 596 bp 5´ of the insulin gene (INS) regulates expression of both INS and the gene encoding insulin-like growth factor 2 (IGF2). The VNTR can be subdivided into two main allele sizes, class I and class III, in Europeans. Class III alleles are associated with reduced expression of INS and IGF2 in the pancreas and placenta6. As lower expression of VNTR class III-associated INS/IGF2 alleles early in fetal development may reduce the chances of survival in utero, the locus is considered a candidate for exhibiting TRD.
Meiotic drive of chromosomal knobs reshaped the maize genome
4349Buckler, ESP-D, T. L.; Buckler, C. S. K.; Dawe, R. K.; Doebley, J. F.; Holtsford, T. P., Genetics, 153:415-426. 1999-01-07 00:00:00.
Meiotic drive is the subversion of meiosis so that particular genes are preferentially transmitted to the progeny. Meiotic drive generally causes the preferential segregation of small regions of the genome; however, in maize we propose that meiotic drive is responsible for the evolution of large repetitive DNA arrays on all chromosomes. A maize meiotic drive locus found on an uncommon form of chromosome 10 [abnormal 10 (Ab10)] may be largely responsible for the evolution of heterochromatic chromosomal knobs, which can confer meiotic drive potential to every maize chromosome. Simulations were used to illustrate the dynamics of this meiotic drive model and suggest knobs might be deleterious in the absence of Ab10. Chromosomal knob data from maize's wild relatives (Zea mays ssp. parviglumis and mexicana) and phylogenetic comparisons demonstrated that the evolution of knob size, frequency, and chromosomal position agreed with the meiotic drive hypothesis. Knob chromosomal position was incompatible with the hypothesis that knob repetitive DNA is neutral or slightly deleterious to the genome. We also show iv that environmental factors and transposition may play a role in the evolution of knobs. Because knobs occur at multiple locations on all maize chromosomes, the combined effects of meiotic drive and genetic linkage may have reshaped genetic diversity throughout the maize genome in response to the presence of Ab10. Meiotic drive may be a major force of genome evolution, allowing revolutionary changes in genome structure and diversity over short evolutionary periods.
Sex ratio distortion in Acraea encedon (Lepidoptera : Nymphalidae) is caused by a male-killing bacterium
4373Jiggins, FMH, G. D. D.; Majerus, M. E. N., Heredity, 81:87-91. 1998-01-11 00:00:00.
Females of the butterfly Acraea encedon produce either entirely female offspring or males and females in an almost 1:1 sex ratio. The sex ratio produced is maternally inherited and was previously attributed to sex chromosome meiotic drive. We report that all-female lineages are associated with low egg-hatching rates and that the trait is cured by antibiotic treatment. We thus reject the hypothesis that this sex ratio bias is caused by a meiotically driven sex chromosome and, instead, propose that it is associated with a maternally inherited bacterium that kills males.
Selfish genes and meiotic drive
4372Hurst, LD, Nature, 391:223-223. 1998-01-10 00:00:00.
Work by Gerald Wilkinson and colleagues3 on stalk-eyed flies (Diopsidae), described on page 276, provides the strongest evidence to date about the nature of some of the genes females prefer. As their name suggests, stalk-eyed flies have their eyes perched on the end of side-projecting stalks (see the cover of this issue). These can reach ridiculous proportions. In two of the species studied, males have considerably greater eye span than females, and male eye span even exceeds body length. In both of these species females show a strong preference for males with a large eye span. In a third species, male eye span was much shorter (indeed no different to female eye span) and there was no female choice.
Wolbachia as a possible means of driving genes into populations
4368Curtis, CFS, S. P., Parasitology, 116:S111-S115. 1998-01-06 00:00:00.
Cytoplasmic incompatibility consists of sterility in cross matings, the crossing type being maternally inherited. It can be explained by the action of Wolbachia symbionts which are transmitted through the egg cytoplasm and leave an imprint on the sperm which prevents it fertilizing unless it is 'rescued' by the action of the same type of Wolbachia in the egg. Thus matings between infected males and uninfected females are sterile, but the reciprocal matings are fertile. Hence uninfected females are at risk of failing to transmit their uninfected cytoplasm if they cross mate, but infected females are at no such risk. Therefore natural selection favours the infected state and in two wild insect populations the infection has been observed spreading. If a gene for inability to transmit malaria could be introduced into Wolbachia and if this could be introduced into Anopheles (where these symbionts appear not to occur naturally), release of a limited number of such insects should trigger a process of displacement of malaria vectors, by the non-vector type. A simple model is used to demonstrate the limitations to this process which would be introduced by immigration.
Selfish DNA and breeding system in flowering plants
4366Burt, AT, R., Proceedings of the Royal Society B-Biological Sciences, 265:141-146. 1998-01-04 00:00:00.
In many species, some individuals carry one or more B chromosomes: extra, or supernumerary chromosomes not part of the normal complement. In most well-studied cases, B's lower the fitness of their carrier and persist in populations only because of accumulation mechanisms analogous to meiotic drive. It has been suggested that such genomic parasites are expected to persist only in outcrossed sexual species, in which uninfected lines of descent can be continuously reinfected; in inbred or asexual species, all selection is between lines of descent, and the genomic parasites are either lost or must evolve into commensals or mutualists. Here we present a simple population genetic model of the effect of outcrossing rate on the frequency of B chromosomes, and find that outcrossing facilitates the spread of parasitic B's, but inhibits the spread of mutualists. Data compiled from the literature on breeding system and B chromosomes of British plants indicate that B's are much more likely to be reported from obligately outcrossed species than inbred species. These results support the ideas that most B chromosomes are parasitic, and that breeding systems play a central role in the biology of selfish genes.
Segregation distortion of the CTG repeats at the myotonic dystrophy locus
4392Chakraborty, RS, D. N.; Deka, R.; Yu, L. M.; Shriver, M. D.; Ferrell, R. E., American Journal of Human Genetics, 59:109-118. 1996-01-10 00:00:00.
Myotonic dystrophy (DM), an autosomal dominant neuromuscular disease, is caused by a CTG-repeat expansion, with affected individuals having greater than or equal to 50 repeats of this trinucleotide, at the DMPK locus of human chromosome 19q13.3. Severely affected individuals die early in life; the milder form of this disease reduces reproductive ability. Alleles in the normal range of CTG repeats are not as unstable as the (CTG)(greater than or equal to 50) alleles. In the DM families, anticipation and parental bias of allelic expansions have been noted. However, data on mechanism of maintenance of DM in populations are conflicting. We present a maximum-likelihood model for examining segregation distortion of CTG-repeat alleles in normal families. Analyzing 726 meiotic events in 95 nuclear families from the CEPH panel pedigrees, we find evidence of preferential transmission of larger alleles (of size less than or equal to 29 repeats) from females (the probability of transmission of larger alleles is .565 +/- 0.03, different from .5 at P approximate to .028). There is no evidence of segregation distortion during male meiosis. We propose a hypothesis that preferential transmission of larger CTG-repeat alleles during female meiosis can compensate for mutational contraction of repeats within the normal allelic size range, and reduced viability and fertility of affected individuals. Thus, the pool of premutant alleles at the DM locus can be maintained in populations, which can subsequently mutate to the full mutation status to give rise to DM.
Meiotic drive an Myotonic Dystrophy – Reply
4404Carey, NJ, K.; Nokelainen, P.; Peltonen, L.; Savontaus, M. L.; Juvonen, V.; Anvret, M.; Grandell, U.; Chotai, K.; Robertson, E.; Middletonprice, H.; Malcolm, S., Nature Genetics, 10:133-133. 1995-01-02 00:00:00.
Myotonic dystrophy (DM) is a trinucleotide disorder and in sub-clinical individuals there is considerable variation in the length of the CTG repeat. Two groups have recently analysed the patterns of segregation of different sized alleles at this locus and both report an excess of the longer version of the allele in the progeny of sub-clinical individuals1•2• This excess they claim to be due to meiotic drive1•2• Our re-analysis of these two studies indic
Meiotic drive at the myotonic dystrophy locus
4413Gennarelli, MD, B.; Baiget, M.; Martorell, L.; Novelli, G., Journal of Medical Genetics, 31:980-980. 1994-01-11 00:00:00.
The mutation underlying myotonic dystrophy (DM, MIM* 160900) is the expansion of a CTG trinucleotide repeat sequence at the 3' untranslated region of a protein kinase gene (MT-PK).' The kinetics of this process is influenced by the sex of the transmitting parent and size of the parental allele.2 Congenital DM (CDM) occurs almost always with maternal transmission. Only two patients with CDM have proven paternal inheritance.5' Maternal transmission is considered to be the result of a large intergenerational increase of the CTG repeat size,7 while repeat length contractions are more likely inherited if the mutated allele is of paternal origin.8 However, the range of expansions is wider for alleles transmitted by fathers with fewer than 100 repeats (range 41 to 95).9 This has suggested a male bias in the generation of new contracted or expanded DM alleles.'° Carey et all' described an unusual segregation of the MT-PK alleles with a CTG number > 19 in healthy persons heterozygous for repeats in the wild type size range, and suggested the possibility of meiotic drive at the DM locus
Meiotic drive on aberrant Chromosome-1 in the mouse is determined by a linked distorter
4418Agulnik, SIS, I. D.; Orlova, G. V.; Ruvinsky, A. O., Genetical Research, 61:91-96. 1993-01-16 00:00:00.
An aberrant chromosome 1 carrying an inverted fragment with two amplified DNA regions was isolated from wild populations of Mus musculus. Meiotic drive favouring the aberrant chromosome was demonstrated for heterozygous females. Its cause was preferential passage of aberrant chromosome 1 to the oocyte. Genetic analysis allowed us to identify a two-component system conditioning deviation from equal segregation of the homologues. The system consists of a postulated distorter and responder. The distorter is located on chromosome 1 distally to the responder, between the ln and Pep-3 genes, and it acts on the responder when in trans position. Polymorphism of the distorters was manifested as variation in their effect on meiotic drive level in the laboratory strain and mice from wild populations.
Meiotic drive for the aberrant Chromosome-1 in mice is determined by a linked distorter
4429Agulnik, SIS, I. D.; Orlova, G. V.; Ruvinsky, A. O., Genetika, 28:47-57. 1992-01-07 00:00:00.
AN aberrant chromosome 1 carrying an inverted fragment with two amplified DNA regions was isolated from natural populations of Mus musculus. A meiotic drive favouring the aberrant chromosome was previously demonstrated for heterozygous females. The cause for this was the preferential passage of the chromosome 1 to the oocyte. Genetic analysis made it possible to identify a two-component system conditioning the deviation from equal segregation of the homologues. The system consists of the postulated distorter and a responder. The distorter is located on the chromosome 1 distally to the responder, between the ln and Pep 3 genes, the former acting on the responder when in the trans position. Polymorphism of the distorters was manifested as variation in their effect on the meiotic drive level in the laboratory strain and mice from natural populations.
Segregation distorters
4451Lyttle, TW, Annual Review of Genetics, 25:511-557. 1991-01-09 00:00:00.
Segregation distorters are genetic elements that exhibit the phenomenon of meiotic drive; that is, the mechanics of the meiotic divisions cause one member of a pair of heterozygous alleles or heteromorphic chromosomes to be transmitted to progeny in excess of the expected Mendelian proportion of 50% ( 1 34 , 1 36). In this review, we refer to these as genic or chromosomal drive, respectively. Genic meiotic drive is initially limited in its impact to the population dynamics of the drive locus itself and those loci fortuitiously in close linkage. Alleles at these latter loci may enjoy indirect drive through genetic hitchhiking, leading eventually to the establishment of drive haplotypes (64). The haplotype may be extended by incorporating chromosome rearrangements that reduce recombination and promote further linkage disequilibrium between the drive locus and more distant modifier loci ( 1 04 , 1 28, 1 64). In the extreme , the haplotype becomes coextensive with the chromosome, leading to a form of chromosomal meiotic drive. For a parent heterozygous for either type of drive system, the statistic k is used to denote the proportion of progeny (and by inference, successful gametes) that carry the allele or chromosome exhibiting segregation distortion. Thus , k can vary from 0 . 5 (Mendelian segregation segregation) to 1 .0 (complete segregation distortion with only one gamete class recovered in the progeny) .
Meiotic drive in female mice heterozygous for the HSR inserts on Chromosome-1
4460Agulnik, SIA, A. I.; Ruvinsky, A. O., Genetical Research, 55:97-100. 1990-01-18 00:00:00.
Chromosome 1 with one or two long insertions has been previously found in natural mouse populations. The inheritance of chromosome 1 with two insertions from the Yakutsk population is analysed in this paper. It was demonstrated that heterozygous females transmit this chromosome to 80–85% of offspring. The observations made at M II, in conjunction with the recombination data, allowed us to conclude that preferential passage of the chromosome 1 with insertions to the oocyte and egg, rather than to the first and second polar bodies at meiosis, is the causative factor of the distorted segregation. A meiotic drive of such potency has not been previously reported for female mammals. The possible mechanism of the drive is discussed.
Meiotic drive of the aberrant Chromosome-1 in the house mouse
4459Agulnik, SIA, A. I.; Ruvinsky, A. O., Genetika, 26:664-669. 1990-01-17 00:00:00.
Animals with aberrant chromosome 1 carrying one or two large insertions were earlier described in natural populations of Mus musculus. In the present work, inheritance of the aberrant chromosome 1 from the Yakutsk population was investigated. It was shown that 80-85% of the progeny from heterozygous females received chromosome 1 with insertions. From chromosomal analysis of blastocytes and oocytes at the MII stage, it was concluded that the preferential distribution of the aberrant chromosome into oocytes during the first and especially, the second meiotic divisions is relevant to the segregation distortion observed. The mechanism of this powerful meiotic drive is discussed.
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.
Population replacement in Culex fatigens by means of cytoplasmic incompatibility. Laboratory experiments with non-overlapping generations
6291C. F. Curtis and T. Adak, Bulletin of the World Health Organization, 51:249-255. 1974-01-08 19:45:42.
Bidirectional cytoplasmic incompatibility in the Culex pipiens complex appears to provide a mechanism for the replacement of a wild population by a strain refractory to filaria or a strain made partly sterile by a translocation. As a preliminary test of the feasibility of the replacement process, various ratios of strains with the cytoplasm of either Delhi or Paris, which are bidirectionally incompatible, were tested in laboratory cages. Where one strain was marked with the ruby-eye gene, this strain always declined in frequency in the next generation. In experiments in which the Paris strain was marked with a male-linked translocation complex, after 2-4 generations of breeding there was complete elimination of either the Paris or the Delhi type depending, as expected, on the relative frequencies of the two types with which the population began. In one experiment a type with Paris cytoplasm devoid of the translocation was found. This type increased in frequency in succeeding generations. The possible causes of origin of this type and its relevance to the practical use of the replacement principle are discussed.
