Scholarly Literature
This is an aggregation of scholarly literature from peer-reviewed journals, bioRxiv , medRxiv and arXiv preprint servers focused on natural and engineered selfish genetic elements and genetic biocontrol. New citations are added as they appear. This content is intended for anyone interested in the scholarly literature on gene drive and genetic biocontrol.
Malaria-Resistant Mosquitoes (Diptera: Culicidae); The Principle is Proven, But Will the Effectors Be Effective?
18710Z. N. Adelman and B. B. Kojin, Journal of Medical Entomology, 58:1997-2005. 2021-05-21 13:50:24.
Over the last few decades, a substantial number of anti-malarial effector genes have been evaluated for their ability to block parasite infection in the mosquito vector. While many of these approaches have yielded significant effects on either parasite intensity or prevalence of infection, just a few have been able to completely block transmission. Additionally, many approaches, while effective against the parasite, also disrupt or alter important aspects of mosquito physiology, leading to corresponding changes in lifespan, reproduction, and immunity. As the most promising approaches move towards field-based evaluation, questions of effector gene robustness and durability move to the forefront. In this forum piece, we critically evaluate past effector gene approaches with an eye towards developing a deeper pipeline to augment the current best candidates.
Optimized CRISPR tools and site-directed transgenesis towards gene drive development in Culex quinquefasciatus mosquitoes
17147X. Feng, V. López Del Amo, E. Mameli, M. Lee, A. L. Bishop, N. Perrimon and V. M. Gantz, Nature Communications, 12:2960. 2021-05-20 13:34:20.
Culex mosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control of Culex mosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking in Culex. Here, we develop a Culex-specific Cas9/gRNA expression toolkit and use site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We show that gRNA scaffold variants improve transgenesis efficiency in both Culex quinquefasciatus and Drosophila melanogaster and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.
Targeting conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus
17054M. Walter, R. Perrone and E. Verdin, Journal of virology, 2021-05-19 13:32:53.
Here, we analyze in cell culture experiments the evolution of resistance in a viral gene drive against human cytomegalovirus. We report that, after an initial invasion of the wildtype population, a drive-resistant population is positively selected over time and outcompetes gene drive viruses. However, we show that targeting evolutionary conserved sequences ensures that drive-resistant viruses acquire long-lasting mutations and are durably attenuated. As a consequence, and even though engineered viruses do not stably persist in the viral population, remaining viruses have a replication defect, leading to a long-term reduction of viral levels. This marks an important step toward developing effective gene drives in herpesviruses, especially for therapeutic applications.<b>Importance</b>The use of defective viruses that interfere with the replication of their infectious parent after co-infecting the same cells - a therapeutic strategy known as viral interference - has recently generated a lot of interest. The CRISPR-based system that we recently reported in herpesviruses represents a novel interfering strategy that causes the conversion of wildtype viruses into new recombinant viruses and drives the native viral population to extinction. In this report, we analyzed how targeted viruses evolved resistance against the technology. Through numerical simulations and cell culture experiments with human cytomegalovirus, we show that, after the initial propagation, a resistant viral population is positively selected and outcompetes engineered viruses over time. We show however that targeting evolutionary conserved sequences ensures that resistant viruses are mutated and attenuated, which leads to a long-term reduction of viral levels. This marks an important step toward the development of novel therapeutic strategies against herpesviruses.
Guidance framework for testing of genetically modified mosquitoes, second edition
17049WHO, WHO-TDR, 2021-05-19 10:41:03.
For more than 2 decades, scientists have been working to harness the promise of molecular biology to develop genetically modified mosquitoes (GMMs) for use as public health tools to prevent the transmission of vector-borne diseases. Responding to a need for additional standards and guidance, the WHO Special Programme for Research and Training in Tropical Diseases (WHO-TDR) and the Foundation for the National Institutes of Health (FNIH) published in 2014 the first WHO Guidance framework for testing genetically modified mosquitoes. This revised version takes into account the technical progress made and lessons learned in this rapidly advancing field of research. Like the original guidance framework, it is intended to provide standards that foster quality and consistency in the processes for developing, testing and regulating these new genetic technologies. Best practices recommended in the 2021 guidance framework will further contribute to the comparability of results and credibility of conclusions in order to facilitate decision-making by countries interested in the potential use of GMMs as public health tools for the control of vector-borne diseases.
Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes
17068R. Carballar-Lejarazú, T. B. Pham, V. Bottino-Rojas, A. Adolfi and A. A. James, J Vis Exp, 2021-05-18 14:30:01.
Control of mosquito-borne pathogens using genetically-modified vectors has been proposed as a promising tool to complement conventional control strategies. CRISPR-based homing gene drive systems have made transgenic technologies more accessible within the scientific community. Evaluation of transgenic mosquito performance and comparisons with wild-type counterparts in small laboratory cage trials provide valuable data for the design of subsequent field cage experiments and experimental assessments to refine the strategies for disease prevention. Here, we present three different protocols used in laboratory settings to evaluate transgene spread in anopheline mosquito vectors of malaria. These include inundative releases (no gene-drive system), and gene-drive overlapping and non-overlapping generation trials. The three trials vary in a number of parameters and can be adapted to desired experimental settings. Moreover, insectary studies in small cages are part of the progressive transition of engineered insects from the laboratory to open field releases. Therefore, the protocols described here represent invaluable tools to provide empirical values that will ultimately aid field implementation of new technologies for malaria elimination.
Genetic Technologies for Sustainable Management of Insect Pests and Disease Vectors
17157S. Grilli, R. Galizi and C. Taxiarchi, Sustainability, 13. 2021-05-18 11:00:25.
Recent advancements in genetic and genome editing research, augmented by the discovery of new molecular tools such as CRISPR, have revolutionised the field of genetic engineering by enabling precise site-specific genome modifications with unprecedented ease. These technologies have found a vast range of applications, including the development of novel methods for the control of vector and pest insects. According to their genetic makeup and engineering, these tools can be tuned to impose different grades of impact on the targeted populations. Here, we review some of the most recent genetic control innovations under development, describing their molecular mechanisms and performance, highlighting the sustainability potentials of such interventions.
Sterile Insect Technique: Successful Suppression of an Aedes aegypti Field Population in Cuba
17151R. Gato, Z. Menendez, E. Prieto, R. Argiles, M. Rodriguez, W. Baldoquin, Y. Hernandez, D. Perez, J. Anaya, I. Fuentes, C. Lorenzo, K. Gonzalez, Y. Campo and J. Bouyer, Insects, 12:13. 2021-05-18 10:40:50.
Here, we describe an open field trial to evaluate the effect of the release of irradiated male Ae. aegypti on a wild population. The pilot trial was carried out in a suburb of Havana and compared the mosquito population density before and after the intervention, in both untreated control and release areas. The wild population was monitored by an ovitrap network, recording frequency and density of eggs as well as their hatch rate. A significant amount of sterility was induced in the field population of the release area, as compared with the untreated control area. The ovitrap index and the mean number of eggs/trap declined dramatically after 12 and 5 weeks of releases, respectively. For the last 3 weeks, no eggs were collected in the treatment area, clearly indicating a significant suppression of the wild target population. We conclude that the sterile males released competed successfully and induced enough sterility to suppress the local Ae. aegypti population.
Experiments confirm a dispersive phenotype associated with a natural gene drive system
17036J.-N. Runge and A. K. Lindholm, Royal Society Open Science, 8:202050. 2021-05-12 11:24:14.
Meiotic drivers are genetic entities that increase their own probability of being transmitted to offspring, usually to the detriment of the rest of the organism, thus ‘selfishly’ increasing their fitness. In many meiotic drive systems, driver-carrying males are less successful in sperm competition, which occurs when females mate with multiple males in one oestrus cycle (polyandry). How do drivers respond to this selection? An observational study found that house mice carrying the t haplotype, a meiotic driver, are more likely to disperse from dense populations. This could help the t avoid detrimental sperm competition, because density is associated with the frequency of polyandry. However, no controlled experiments have been conducted to test these findings. Here, we confirm that carriers of the t haplotype are more dispersive, but we do not find this to depend on the local density. t-carriers with above-average body weight were particularly more likely to disperse than wild-type mice. t-carrying mice were also more explorative but not more active than wild-type mice. These results add experimental support to the previous observational finding that the t haplotype affects the dispersal phenotype in house mice, which supports the hypothesis that dispersal reduces the fitness costs of the t.
CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion
17008Z. Li, N. Marcel, S. Devkota, A. Auradkar, S. M. Hedrick, V. M. Gantz and E. Bier, Nature Communications, 12:2625. 2021-05-11 12:45:39.
CRISPR-based active genetic elements, or gene-drives, copied via homology-directed repair (HDR) in the germline, are transmitted to progeny at super-Mendelian frequencies. Active genetic elements also can generate widespread somatic mutations, but the genetic basis for such phenotypes remains uncertain. It is generally assumed that such somatic mutations are generated by non-homologous end-joining (NHEJ), the predominant double stranded break repair pathway active in somatic cells. Here, we develop CopyCatcher systems in Drosophila to detect and quantify somatic gene conversion (SGC) events. CopyCatchers inserted into two independent genetic loci reveal unexpectedly high rates of SGC in the Drosophila eye and thoracic epidermis. Focused RNAi-based genetic screens identify several unanticipated loci altering SGC efficiency, one of which (c-MYC), when downregulated, promotes SGC mediated by both plasmid and homologous chromosome-templates in human HEK293T cells. Collectively, these studies suggest that CopyCatchers can serve as effective discovery platforms to inform potential gene therapy strategies.
A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase
17027H. Gao, L. Bai, Y. M. Jiang, W. Huang, L. L. Wang, S. G. Li, G. D. Zhu, D. Q. Wang, Z. H. Huang, X. S. Li, J. Cao, L. B. Jiang, M. Jacobs-Lorena, S. Zhan and S. B. Wang, Nature Microbiology, 25. 2021-05-06 11:00:53.
The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field. The symbiotic bacterium Serratia ureilytica can disseminate through mosquito populations and render mosquitoes resistant to Plasmodium infection by secreting an antimalarial lipase.
Sterile Insect Technique Programme against Mediterranean Fruit Fly in the Valencian Community (Spain)
16965I. Plá, J. García de Oteyza, C. Tur, M. Á. Martínez, M. C. Laurín, E. Alonso, M. Martínez, Á. Martín, R. Sanchis, M. C. Navarro, M. T. Navarro, R. Argilés, M. Briasco, Ó. Dembilio and V. Dalmau, Insects, 12. 2021-05-04 15:09:26.
The Mediterranean fruit fly, Ceratitis capitata (Wied.), is an endemic pest in fruit-growing areas of the Spanish Mediterranean coast. In the Valencian Community, it represents a serious problem in the cultivation of citrus and numerous species of fruit, such as peach, cherry, apricot, persimmon, etc. For over 50 years, the Department of Agriculture of Valencia has led, promoted, and carried out a C. capitata control programme to protect crops, especially citrus fruits, because this community is the largest national producer and the leading region for fresh citrus exports in the world. Traditionally, pest control has been based on the use of insecticides. However, a reduction of more than 90% of a target wild population was achieved in the frame of a pilot integrated pest management (IPM) project based on the sterile insect technique (SIT), which was implemented from 2003 to 2006. Based on this successful result, in 2007 the Department of Agriculture of Valencia initiated an area-wide integrated pest management (AW-IPM) programme for the suppression of C. capitata, using the SIT as the primary control method. Complementary activities are implemented periodically in hotspots and during different time periods depending on the pest population dynamics. As a result, there has been a reduction of more than 90% in the use of insecticides by aerial means to control C. capitata, as well as a growth trend in exports of citrus and fresh fruits from the Valencian Community in recent years. This paper provides a historical review of the Valencian programme and briefly describes how technological innovations and decision-making tools have contributed to programme efficiency.
Stable isotopes for reliable identification of wild and mass-reared Queensland fruit flies in sterile insect technique programs
17031B. Mainali, A. S. Andrew, P. W. Taylor and P. Rempoulakis, Journal of Pest Science, 14. 2021-05-04 11:12:25.
Queensland fruit fly is one of the most economically important horticultural pests in Australia. Sterile insect technique (SIT) is now being reconsidered and upscaled to combat this pest so reliable discrimination of released sterile Q-flies from wild flies in monitoring traps is important for effective SIT operations. Stable isotopes provide a permanent chemical marker to discriminate sterile and wild flies when dye marking is unclear. In this study, we compared the isotopic ratios of carbon and nitrogen between Q-flies reared on different larval diets and wild flies collected from diverse locations in Australia and New Caledonia. Finally, we conducted a release-recapture study to corroborate differences in stable isotope C and N ratios in laboratory-reared and wild Q-flies. The delta N-15 values obtained from wild and laboratory Q-flies showed high variability that is likely related to the food source of the larval and/or adult stage and do not offer an effective means to discriminate between sterile and wild Q-flies. The delta C-13 values of examined wild Q-flies ranged from - 27.46 to - 24.37 parts per thousand VPDB, whereas those from laboratory-reared, released and recaptured Q-flies ranged from - 25.73 to - 19.26 parts per thousand VPDB. Differences in delta C-13 values resulted in 100% correct classification of wild flies and 96.88% correct classification of released flies. Measurements of intrinsic delta C-13 values offer a precise tool to discriminate between sterile and wild Q-flies in SIT programs, regardless of the composition of the larval or adult pre-release diets.
Living in the endosymbiotic world of Wolbachia: A centennial review
17794R. Kaur, J. D. Shropshire, K. L. Cross, B. Leigh, A. J. Mansueto, V. Stewart, S. R. Bordenstein and S. R. Bordenstein, Cell Host and Microbe, 29:879-893. 2021-05-03 20:31:30.
The most widespread intracellular bacteria in the animal kingdom are maternally inherited endosymbionts of the genus Wolbachia. Their prevalence in arthropods and nematodes worldwide and stunning arsenal of parasitic and mutualistic adaptations make these bacteria a biological archetype for basic studies of symbiosis and applied outcomes for curbing human and agricultural diseases. Here, we conduct a summative, centennial analysis of living in the Wolbachia world. We synthesize literature on Wolbachia's host range, phylogenetic diversity, genomics, cell biology, and applications to filarial, arboviral, and agricultural diseases. We also review the mobilome of Wolbachia including phage WO and its essentiality to hallmark reproductive phenotypes in arthropods. Finally, the Wolbachia system is an exemplar for discovery-based science education using biodiversity, biotechnology, and bioinformatics lessons. As we approach a century of Wolbachia research, the interdisciplinary science of this symbiosis stands as a model for consolidating and teaching the integrative rules of endosymbiotic life.
Genetic Manipulation of Ticks: A Paradigm Shift in Tick and Tick-Borne Diseases Research
17164A. Nuss, A. Sharma and M. Gulia-Nuss, Frontiers in Cellular and Infection Microbiology, 11:7. 2021-05-02 19:18:28.
Ticks are obligate hematophagous arthropods that are distributed worldwide and are one of the most important vectors of pathogens affecting humans and animals. Despite the growing burden of tick-borne diseases, research on ticks has lagged behind other arthropod vectors, such as mosquitoes. This is largely because of challenges in applying functional genomics and genetic tools to the idiosyncrasies unique to tick biology, particularly techniques for stable genetic transformations. CRISPR-Cas9 is transforming non-model organism research; however, successful germline editing has yet to be accomplished in ticks. Here, we review the ancillary methods needed for transgenic tick development and the use of CRISPR/Cas9, the most promising gene-editing approach, for tick genetic transformation.
Mechanistically comparing reproductive manipulations caused by selfish chromosomes and bacterial symbionts
16958E. Dalla Benetta, O. S. Akbari and P. M. Ferree, Heredity, 126:707-716. 2021-05-01 14:52:23.
Insects naturally harbor a broad range of selfish agents that can manipulate their reproduction and development, often leading to host sex ratio distortion. Such effects directly benefit the spread of the selfish agents. These agents include two broad groups: bacterial symbionts and selfish chromosomes. Recent studies have made steady progress in uncovering the cellular targets of these agents and their effector genes. Here we highlight what is known about the targeted developmental processes, developmental timing, and effector genes expressed by several selfish agents. It is now becoming apparent that: (1) the genetic toolkits used by these agents to induce a given reproductive manipulation are simple, (2) these agents target sex-specific cellular processes very early in development, and (3) in some cases, similar processes are targeted. Knowledge of the molecular underpinnings of these systems will help to solve long-standing puzzles and provide new tools for controlling insect pests.
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.
Modeling and analysis of the implementation of the Wolbachia incompatible and sterile insect technique for mosquito population suppression.
17098B. Zheng, J. S. Yu and J. Li, Siam Journal on Applied Mathematics, 81:718-740. 2021-04-29 13:06:06.
Mathematical analysis may offer guidance in designing effective mass release strategies for the area-wide application of this Wolbachia incompatible and sterile insect technique in the future. The two most crucial concerns in designing release strategies are how often and in what amount should Wolbachia-infected mosquitoes be released in order to guarantee population suppression. Motivated by the experimental data from the Guangzhou mosquito factory and the release strategy implemented on two islands, we formulate and analyze a mosquito population suppression model considering the situation for the release period T less than the sexual lifespan of Wolbachia-infected males. We define release amount thresholds g(1)* and g(2)* with g(1)* < g(2)*. When the release amount c satisfies c >= g(2)*, population suppression is always achievable, as is mathematically manifested by the global asymptotic stability of the origin. However, when c is an element of (0, g(1)*], we find that suppression can be achieved only if the initial wild mosquito population is small enough. This is mathematically proved by the local asymptotic stability of the origin, together with the existence of exactly two T-periodic solutions, one of which is asymptotically stable and the other of which is unstable, with T being the waiting period between two consecutive releases. For c is an element of (g(1)*, g(2)*), we find sufficient conditions on the nonexistence of T-periodic solution, and the existence of at most two T-periodic solutions.
Selection of Sites for Field Trials of Genetically Engineered Mosquitoes with Gene Drive
16932G. C. Lanzaro, M. Campos, M. Crepeau, A. Cornel, A. Estrada, H. Gripkey, Z. Haddad, A. Kormos, S. Palomares and W. Sharpee, bioRxiv, 2021.04.28.441877. 2021-04-28 15:53:05.
Novel malaria control strategies using genetically engineered mosquitoes (GEMs) are on the horizon. Population modification is one approach wherein mosquitoes are engineered with genes rendering them refractory to the malaria parasite coupled with a low-threshold, Cas9-based gene drive. When released into a wild vector population, GEMs preferentially transmit these beneficial genes to their offspring, ultimately modifying a vector population into a non-vector one. Deploying this technology awaits evaluation including ecologically contained field trials. Here, we consider a process for site selection, the first critical step in designing a trial. Our goal is to identify a site that maximizes prospects for success, minimizes risk, and serves as a fair, valid, and convincing test of efficacy and impacts of a GEM product intended for large-scale deployment in Africa. We base site selection on geographical, geological, and biological, rather than social or legal, criteria. We recognize the latter as critically important but not preeminent. We propose physical islands as being the best candidates for a GEM field trial and present an evaluation of 22 African islands. We consider geographic and genetic isolation, biological complexity, island size, topography, and identify two island groups that satisfy key criteria for ideal GEM field trial sites.Competing Interest StatementThe authors have declared no competing interest.
“Maskandi experience”: exploring the use of a cultural song for community engagement in preparation for a pilot Sterile Insect Technique release programme for malaria vector control in KwaZulu-Natal Province, South Africa 2019
17029P. N. Manana, S. Jewett, J. Zikhali, D. Dlamini, N. Mabaso, Z. Mlambo, R. Ngobese and G. Munhenga, Malaria Journal, 20:11. 2021-04-28 11:06:19.
Background An assessment of the Sterile Insect Technique (SIT) as a complementary malaria vector control tool, is at an advanced stage in South Africa. The technique involves the release of laboratory-reared sterilized male mosquitoes of the major malaria vector Anopheles arabiensis, raising social, ethical and regulatory concerns. Therefore, its implementation largely depends on community participation and acceptance. Against this background, it is critical that robust and effective community strategies are developed. This study describes the development of a cultural song to engage the community and increase awareness on SIT and malaria control in KwaZulu-Natal, South Africa. Methods An exploratory concurrent mixed-methods study was conducted to get opinions about the effectiveness of a cultural song developed to engage communities and increase acceptability of the SIT technology. Two self-administered surveys (expert and community) were conducted. Additionally, more in depth opinions of the song and its effectiveness in conveying the intended information were investigated through three community dialogue sessions with community members in the study area. Results A total of 40 experts and 54 community members participated in the survey. Four themes were identified in relation to the appropriateness and effectiveness of the song, with a fifth theme focused on recommendations for adaptations. Overall, the song was well received with the audience finding it entertaining and informative. Responses to unstructured questions posed after the song showed an increase in the knowledge on malaria transmission and SIT technology. In particular, the explanation that male mosquitoes do not bite allayed anxiety and fears about the SIT technology. Conclusion The song was deemed both culturally appropriate and informative in engaging community members about the SIT technology. It proved useful in promoting health messages and conveying SIT technology as a complementary malaria vector control tool. With minor adaptations, the song has potential as an area-wide community engagement tool in areas targeted for sterile male releases.
Does Gene Technology Offer Potential to Wipe Out Malaria?
16845Anonymous, AFIDEP, 2021-04-25 13:15:13.
The persisting high numbers of Malaria deaths and illnesses mean that the current tools will not get us to zero Malaria. For this reason, experts have continued to explore new tools for Malaria elimination. The gene drive technology is one of the tools being explored for Malaria elimination in Africa. The technology, developed in the past decade, enables precise editing of the genes of living organisms. For Malaria, the technology could be applied to modify the genes of Malaria-causing mosquitoes (the Anopheles) to either reduce their survival or deactivate genes that enable them to carry the Malaria parasite. If successfully applied, scientists believe that gene drive mosquitoes could significantly accelerate the path to Malaria elimination, or zero Malaria. In 2017, the African Union recognized the potential of the gene drive technology in controlling and eliminating Malaria on the continent, and committed to invest in the development and regulation of the technology. This commitment is being implemented by the African Union Development Agency (AUDA/NEPAD), which is currently spearheading efforts to build capacity and support countries to establish the necessary regulatory framework for guiding the research to test the gene drive technology for elimination of Malaria on the continent.
A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist
16970D. A.-O. Milner, J. A.-O. Wideman, C. A.-O. Stairs, C. D. Dunn and T. A.-O. Richards, PLoS Biology, 2021-04-23 15:33:12.
The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss. Therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. In the mitochondrial genome of a marine heterotrophic katablepharid protist, we identify a functional type II restriction modification (RM) system originating from a horizontal gene transfer (HGT) event involving bacteria related to flavobacteria. This RM system consists of an HpaII-like endonuclease and a cognate cytosine methyltransferase (CM). We demonstrate that these proteins are functional by heterologous expression in both bacterial and eukaryotic cells. These results suggest that a mitochondrion-encoded RM system can function as a toxin-antitoxin selfish element, and that such elements could be co-opted by eukaryotic genomes to drive biased organellar inheritance. FAU - Milner, David S
Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers
16833F. R. Finseth, T. C. Nelson and L. Fishman, PLOS Genetics, 17:e1009418. 2021-04-22 14:16:46.
Centromeres must mediate faithful chromosomal transmission during cell division and sexual reproduction, but both the DNA and protein components of centromeres diverge rapidly across species. The selfish centromere model argues that this paradoxical diversity results from a genetic conflict between centromeric DNA variants driving through female meiosis to gain over-transmission and kinetochore proteins co-evolving to re-establish Mendelian segregation. We use whole genome sequencing and genetic crossing experiments to demonstrate active evolutionary interactions between a selfish centromere and a key kinetochore protein (CenH3A) in the wildflower Mimulus guttatus. We show that both inter-specific and intra-population differences in CenH3A affect centromeric drive in hybrids, and that adaptive evolution of CenH3A has followed the recent and costly spread of the driver in a wild population. This work provides novel empirical support for the proposed antagonistic co-evolution of the DNA and protein components of centromeres, with important consequences for understanding cellular function, individual fitness, and species divergence.
Development of Sterile Insect Technique for Control of the European Grapevine Moth, Lobesia botrana, in Urban Areas of Chile
16849G. S. Simmons, M. C. Salazar Sepulveda, E. A. Fuentes Barrios, M. Idalsoaga Villegas, R. E. Medina Jimenez, A. R. Garrido Jerez, R. Henderson and H. Donoso Riffo, Insects, 12. 2021-04-22 13:20:22.
The European grapevine moth, a Palearctic pest, was first detected in the Americas in 2008. Its establishment in Chile presented production and export issues for grapes and other fruits, and a national control campaign was launched. Urban areas next to agricultural production areas were recognized as a challenge for effective control. In 2015, a SIT laboratory was established in Arica, Chile to evaluate its potential for urban control. Progress included the development and evaluation of artificial diets, a mass-rearing of 75,000 moths/week, confirmation of 150 Gy as an operational dose for inherited sterility, and releases of sterile moths in a 25 ha urban area next to fruit production areas. Season-long releases demonstrated that high overflooding ratios were achieved early in the season but decreased with a large increase in the wild moth population. Sterile moth quality was consistently high, and moths were observed living in the field up to 10 days and dispersing up to 800 m. Recommendations for further development of the SIT include conducting cage and field studies to evaluate overflooding ratios and mating competitiveness, measuring of infestation densities in release and no-release areas, and conducting trials to evaluate combining SIT with compatible integrated pest management (IPM) tactics such as fruit stripping and use of mating disruption.
CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues
17324R. Piergentili, A. Del Rio, F. Signore, F. U. Ronchi, E. Marinelli and S. Zaami, Cells, 10:24. 2021-04-21 12:06:42.
The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man. During the years this technique has been applied in several fields, such as agriculture for crop upgrade and breeding including the creation of allergy-free foods, for eradicating pests, for the improvement of animal breeds, in the industry of bio-fuels and it can even be used as a basis for a cell-based recording apparatus. Possible applications in human health include the making of new medicines through the creation of genetically modified organisms, the treatment of viral infections, the control of pathogens, applications in clinical diagnostics and the cure of human genetic diseases, either caused by somatic (e.g., cancer) or inherited (mendelian disorders) mutations. One of the most divisive, possible uses of this system is the modification of human embryos, for the purpose of preventing or curing a human being before birth. However, the technology in this field is evolving faster than regulations and several concerns are raised by its enormous yet controversial potential. In this scenario, appropriate laws need to be issued and ethical guidelines must be developed, in order to properly assess advantages as well as risks of this approach. In this review, we summarize the potential of these genome editing techniques and their applications in human embryo treatment. We will analyze CRISPR-Cas limitations and the possible genome damage caused in the treated embryo. Finally, we will discuss how all this impacts the law, ethics and common sense.
Estimates of the population size and dispersal range of Anopheles arabiensis in Northern KwaZulu-Natal, South Africa: implications for a planned pilot programme to release sterile male mosquitoes
17062M. L. Kaiser, O. R. Wood, D. Damiens, B. D. Brooke, L. L. Koekemoer and G. Munhenga, Parasites and Vectors, 14:18. 2021-04-19 13:57:18.
The Anopheles gambiae complex and An. funestus group species made up the majority of wild collections along with other anophelines. The An. arabiensis population size was estimated to be between 550 and 9500 males per hectare depending on time of year, weather conditions and method used. Average dispersal distance of marked males ranged from 58 to 86 m. Marked males were found in swarms with wild males, indicating that laboratory-reared males are able to locate and participate in mating swarms. Conclusions It was logistically feasible to conduct mark-release-recapture studies at the current scale. The population size estimates obtained may provide a guideline for the initial number of males to use for a pending SIT pilot trial. It is promising for future SIT trials that laboratory-reared marked males participated in natural swarms, appearing at the right place at the right time.
Engineered sex ratio distortion by X-shredding in the global agricultural pest Ceratitis capitata
16837A. Meccariello, F. Krsticevic, R. Colonna, G. Del Corsano, B. Fasulo, P. A. Papathanos and N. Windbichler, BMC Biology, 19:78. 2021-04-16 14:29:21.
Genetic sex ratio distorters are systems aimed at effecting a bias in the reproductive sex ratio of a population and could be applied for the area-wide control of sexually reproducing insects that vector disease or disrupt agricultural production. One example of such a system leading to male bias is X-shredding, an approach that interferes with the transmission of the X-chromosome by inducing multiple DNA double-strand breaks during male meiosis. Endonucleases targeting the X-chromosome and whose activity is restricted to male gametogenesis have recently been pioneered as a means to engineer such traits.
The Insect Pest Control Laboratory of the Joint FAO/IAEA Programme: Ten Years (2010–2020) of Research and Development, Achievements and Challenges in Support of the Sterile Insect Technique
16702M. J. B. Vreysen, A. M. M. Abd-Alla, K. Bourtzis, J. Bouyer, C. Caceres, C. de Beer, D. Oliveira Carvalho, H. Maiga, W. Mamai, K. Nikolouli, H. Yamada and R. Pereira, Insects, 12. 2021-04-13 15:29:17.
The Joint FAO/IAEA Centre (formerly called Division) of Nuclear Techniques in Food and Agriculture was established in 1964 and its accompanying laboratories in 1961. One of its subprograms deals with insect pest control, and has the mandate to develop and implement the sterile insect technique (SIT) for selected key insect pests, with the goal of reducing the use of insecticides, reducing animal and crop losses, protecting the environment, facilitating international trade in agricultural commodities and improving human health.
Introduction of a cold sensitivity-conferring mutation into the RTA-Bddsx hybrid system of Bactrocera dorsalis for establishment of a thermally controllable homozygous line
17327S. M. Dai, C. Y. Huang and C. Chang, Pest Management Science, 7. 2021-04-10 14:40:01.
BACKGROUND For efficient control of the economically important fruit pest Bactrocera dorsalis, a hybrid system combining ricin toxicity and sex-related alternative splicing of the doublesex gene has been developed. This system exhibits the expected female-specific lethal effect; however, the transgenic females do not survive, making it difficult to raise stable homozygous lines. Since modification of ricin toxin A chain (RTA) through a single-residue change (Gly(212) > Arg(212)) leads to cold-sensitive posttranslational repression of its toxicity, we utilized this unique property to obtain RTA-Bddsx females that survive at low temperature for line maintenance. RESULTS In transient expression experiments using embryonic injection, two groups treated with RTAcs-derived DNA (LERQcs and RTAcs) exhibited temperature-dependent effects. The toxicity was higher at 29 degrees C than at 18 degrees C. The proportion of males was close to 50% at 18 degrees C in all the tested groups except LERQcs-treated flies, which exhibited a high proportion of males (over 70%) at 29 degrees C. The results indicate the cold-sensitive responses of RTA and further suggest a female-specific lethal effect. Subsequently, 14 putative RTAcs-Bddsx transgenic Ds-Red(+) G(1) males were identified, and female-specific lethal effects were observed in Ds-Red(+) G(2) and G(3) lines under cultivation at 29 degrees C but not at 18 degrees C. The male ratio can be increased to up to 95% in G(3) line 001, indicating that RTAcs functions well in B. dorsalis. CONCLUSION The improved RTAcs-Bddsx system with conditional toxicity represents a novel and promising step toward the practical control of B. dorsalis.
Evidence for natural hybridization and novel Wolbachia strain superinfections in the Anopheles gambiae complex from Guinea
16990C. L. Jeffries, C. Cansado-Utrilla, A. H. Beavogui, C. Stica, E. K. Lama, M. Kristan, S. R. Irish and T. Walker, Royal Society Open Science, 8:18. 2021-04-07 14:55:09.
Wolbachia, a widespread bacterium which can influence mosquito-borne pathogen transmission, has recently been detected within Anopheles (An.) species that are malaria vectors in Sub-Saharan Africa. Although studies have reported Wolbachia strains in the An. gambiae complex, apparent low density and prevalence rates require confirmation. In this study, wild Anopheles mosquitoes collected from two regions of Guinea were investigated. In contrast with previous studies, RNA was extracted from adult females (n = 516) to increase the chances for the detection of actively expressed Wolbachia genes, determine Wolbachia prevalence rates and estimate relative strain densities. Molecular confirmation of mosquito species and Wolbachia multilocus sequence typing (MLST) were carried out to analyse phylogenetic relationships of mosquito hosts and newly discovered Wolbachia strains. Strains were detected in An. melas (prevalence rate of 11.6%-16/138) and hybrids between An. melas and An. gambiae sensu stricto (prevalence rate of 40.0%-6/15) from Senguelen in the Maferinyah region. Furthermore, a novel high-density strain, termed wAnsX, was found in an unclassified Anopheles species. The discovery of novel Wolbachia strains (particularly in members, and hybrids, of the An. gambiae complex) provides further candidate strains that could be used for future Wolbachia-based malaria biocontrol strategies.
CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus
16674C. Quinn, A. Anthousi, C. Wondji and T. Nolan, bioRxiv, 2021.03.31.437891. 2021-03-31 13:57:08.
We describe herein an optimised transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in An. funestus.Competing Interest StatementThe authors have declared no competing interest.
Determining the Sterilization Doses under Hypoxia for the Novel Black Pupae Genetic Sexing Strain of Anastrepha fraterculus (Diptera, Tephritidae)
16672P. D. Giustina, T. Mastrangelo, S. Ahmad, G. Mascarin and C. Caceres, Insects, 12. 2021-03-30 13:38:24.
Our study reports for the first time the dose-sterility response under hypoxia for two different A. fraterculus strains. The pupae were derived from a bisexual strain (a Brazilian-1 population) and a recently developed genetic sexing strain (GSS-89). Two hours prior to irradiation, pupae were transferred to sealed glass bottles and irradiated when oxygen concentration was below 3%. Four types of crosses with nonirradiated flies of the bisexual strain were set to assess sterility for each radiation dose. For males from both strains, Weibull dose–response curves between radiation doses and the proportion of egg hatch, egg-to-pupa recovery, and recovery of adults were determined. The GSS males revealed high sterility/mortality levels compared to males from the bisexual strain at doses < 40 Gy, but a dose of 74 Gy reduced egg hatch by 99% regardless of the male strain and was considered the sterilizing dose. The fertility of irradiated females was severely affected even at low doses under hypoxia.
Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa
16668J. B. Connolly, J. D. Mumford, S. Fuchs, G. Turner, C. Beech, A. R. North and A. Burt, Malaria Journal, 20:170. 2021-03-29 18:49:26.
Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus (dsxFCRISPRh) has recently been shown to increase rapidly in frequency in, and suppress, caged laboratory populations of the malaria mosquito vector Anopheles gambiae. Here, problem formulation, an initial step in environmental risk assessment (ERA), was performed for simulated field releases of the dsxFCRISPRh transgene in West Africa.
Sterile Insect Technique in an Integrated Vector Management Program against Tiger Mosquito Aedes albopictus in the Valencia Region (Spain): Operating Procedures and Quality Control Parameters
16663C. Tur, D. Almenar, S. Benlloch-Navarro, R. Argilés-Herrero, M. Zacarés, V. Dalmau and I. Pla, Insects, 12. 2021-03-23 14:20:04.
The Agriculture Department of the Valencian Region is promoting an ongoing pilot project to evaluate the efficacy of an integrated vector management program (IVM) based on the use of the SIT as the main method of control. The laboratory studies for evaluating the entomological efficacy of SIT through the phased conditional testing process recommended by World Health Organization and the International Atomic Energy Agency (WHO-IAEA) are addressed. This study describes the routine operating procedures and quality control parameters for the medium-scale rearing of sterile male A. albopictus. More than 15 million sterile males have been produced and released in an area of 80 ha between 2018 and 2020. Of the initial L1 larvae, we recovered 17.2% of male pupae after sex sorting to be sterilized and released on the field, while the rest of the pupae remained available to maintain the rearing colony. The residual percentage of females after sex sorting was on average 0.17%. The obtained values in terms of production and quality control as well as the proposed rearing methodology can be useful for designing a medium-scale mosquito-rearing pipeline.
Experimenting with co-development: a qualitative study of gene drive research for malaria control in Mali
16639S. Hartley, K. Ledingham, R. Owen, S. Leonelli, S. Diarra and S. Diop, Social Science and Medicine, 2021-03-21 14:37:21.
Our findings suggest co-development is opening up previously expert-dominated spaces as researchers attempt to take responsibility for the societal implications of their work. However, its main function is as a project management tool to enable and instrumentally support technological development, field trials and eventual deployment. This function extends into areas which are traditionally the responsibility of the state, such as regulatory development, facilitated by Mali’s fragile political and economic situation. Paradoxically, co-development simultaneously depoliticises gene drive, masking power relations and closing down substantive debate and agency. Characterised by extreme poverty, conflict and weak institutions, Mali may become a site for technological experimentation where there is little interrogation of gene drive or its governance.
Ethics of Genome Editing
16622European Group on Ethics, European Group on Ethics in Science and New Technologies, 2021-03-19 18:16:09.
This Opinion addresses the profound ethical questions raised and revived by them. It analyses various domains of application, from human health to animal experimentation, from livestock breeding to crop variety and to gene drives. With its wide view across areas, it identifies underlying and overarching issues that deserve our concerted attention, among them, the different meanings that ought to be attributed to humanness, naturalness or diversity. This enables conclusions that provide panoramic perspectives complementing narrower, area-specific analyses. In the same vein, the Opinion is concerned with the global dimension of genome editing and its regulation and formulates recommendations with a particular focus on the international level.
Evaluating unintended consequences of intentional species introductions and eradications for improved conservation management
16631D. E. Pearson, T. J. Clark and P. G. Hahn, Conserv Biol, 2021-03-19 14:52:01.
We conducted a global literature review of these conservation actions to quantify how often unintended outcomes occur and to elucidate their underlying causes. We found that studies reported intended outcomes in 51% of cases, a combination of intended outcomes and unintended outcomes in 26% of cases, and strictly unintended outcomes in 10% of cases. Hence, unintended outcomes were reported in 36% of all cases evaluated. In evaluating overall conservations outcomes (weighing intended vs unintended effects), some unintended effects are fairly innocuous relative to successful conservation objectives whereas others result in serious unintended consequences in recipient communities. Importantly, we also found that studies that assessed a greater number of community interactions with the target species were more likely to report unintended outcomes, suggesting that unintended consequences may be under-reported due to insufficient vetting.
The ethical scientist in a time of uncertainty
16620L. Zoloth, Cell, 184:1430-1439. 2021-03-18 17:59:56.
Using the example of gene drives for malaria control to explore the problem of deep uncertainty in biomedical research, I argue that profound uncertainty is an essential feature. Applying the language and presumptions of the discipline of philosophical ethics, I describe three types of uncertainty that raise ethical challenges in scientific research. Rather than mitigate these challenges with excessive precautions and limits on progress, I suggest that researchers can cultivate classic values of veracity, courage, humility, and fidelity in their research allowing science to proceed ethically under conditions of deep uncertainty.
Driving to Safety: CRISPR-Based Genetic Approaches to Reducing Antibiotic Resistance
16614E. Bier and V. Nizet, Trends in Genetics, 2021-03-18 17:34:35.
The complex and challenging problem of reducing antibiotic resistance (AR) requires a network of both societal and science-based solutions to preserve the most lifesaving pharmaceutical intervention known to medicine. In addition to developing new classes of antibiotics, it is essential to safeguard the clinical efficacy of existing drugs. In this review, we examine the potential application of novel CRISPR-based genetic approaches to reducing AR in both environmental and clinical settings and prolonging the utility of vital antibiotics.
Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control
16629S. M. O'Loughlin, A. J. Forster, S. Fuchs, T. Dottorini, T. Nolan, A. Crisanti and A. Burt, G3-Genes Genomes Genetics, 2021-03-18 14:15:51.
Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were found across the alignment, with a maximum length of 164 bp. Length-corrected gene ontology analysis revealed that genes containing Anopheles ultra-conserved elements were over-represented in categories with structural or nucleotide binding functions. Known insect transcription factor binding sites were found in 48% of intergenic Anopheles ultra-conserved elements. When we looked at the genome sequences of 1142 wild-caught mosquitoes we found that 15% of the Anopheles ultra-conserved elements contained no polymorphisms. Our list of Anopheles ultra-conserved elements should provide a valuable starting point for the selection and testing of new targets for gene-drive modification in the mosquitoes that transmit malaria.
Meiotic Cas9 expression mediates genotype conversion in the male and female mouse germline.
16618A. J. Weitzel, H. A. Grunwald, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper, 2021.03.16.435716, 2021-03-17 17:52:21.
We previously showed that such a system of genotype conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double strand DNA break is feasible in the female mouse germline. In the male germline, however, all double strand breaks were instead repaired by end joining mechanisms to form an 'insertion/deletion' (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homology directed repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate genotype conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient double strand DNA break formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of genotype conversion and further increase the rate of 'super-Mendelian' inheritance from both male and female mice.Competing Interest StatementVMG, SMH, EB, and KLC hold advisory board positions with Synbal, Inc. All other authors declare that they have no competing interests.
Differentiated impacts of human interventions on nature: Scaling the conversation on regulation of gene technologies
18750J. A. Heinemann, D. J. Paull, S. Walker and B. Kurenbach, Elementa: Science of the Anthropocene, 9. 2021-03-17 13:35:29.
Biotechnology describes a range of human activities in medicine, agriculture, and environmental management. One biotechnology in particular, gene technology, continues to evolve both in capacity and potential to benefit and harm society. The purpose of this article is to offer a policy bridge from unproductive descriptions of gene technology to useful methods for identifying sources of significant biological and socioeconomic risk in complex food systems. Farmers and the public could be voluntarily and involuntarily interacting with new techniques of genome editing and gene silencing in entirely new ways, limiting the usefulness of previous gene technology histories to predict safety. What we believe is a more consistent, verifiable, and practical approach is to identify the critical control points that emerge where the scale effects of a human activity diverge between risk and safety. These critical control points are where technical experts can collaborate with publics with different expertise to identify and manage the technology. The use of technical terminology describing biochemical-level phenomena discourages publics that are not technical experts from contesting the embedded cultural perspectives and uncertainty in “scientific” concepts and prejudice the risk discourse by ignoring other issues of significance to society. From our perspective as gene technologists, we confront the use of pseudo-scale language in risk discourse and propose an escape path from clashes over whether risks that arise spontaneously (from nature) can be perfectly mimicked by gene technology to a discussion on how to best control the risks created by human activity. Scale is conceptually implicit and explicit in gene technology regulation, but there is no agreement about what scales are most useful to managing risk and social expectations. Both differentiated governance (risk-tiered) and responsible research and innovation models could accommodate the critical control points mechanism that we describe.
Genetically Encoded CRISPR components Yield Efficient Gene Editing in the Invasive Pest, Drosophila suzukii
16602N. P. Kandul, E. J. Belikoff, J. Liu, A. Buchman, F. Li, A. Yamamoto, T. Yang, I. Shriner, M. J. Scott and O. Akbari, bioRxiv, 2021.03.15.435483. 2021-03-16 18:28:51.
Here we have developed transgenic strains that encode three different terminators and four different promoters to express Cas9 in both the soma and/or germline of SWD. The Cas9 lines were evaluated through genetic crossing to transgenic lines that encode single guide RNAs targeting the conserved X-linked yellow body and white eye genes. We find that several Cas9/gRNA lines display very high editing capacity. Going forward, these tools will be instrumental for evaluating gene function in SWD and may provide tools useful for the development of new genetic strategies for control of this invasive species.
Ugandan stakeholder hopes and concerns about gene drive mosquitoes for malaria control: new directions for gene drive risk governance
16600S. Hartley, R. D. J. Smith, A. Kokotovich, C. Opesen, T. Habtewold, K. Ledingham, B. Raymond and C. B. Rwabukwali, Malaria Journal, 20:149. 2021-03-16 18:12:21.
The African Union’s High-Level Panel on Emerging Technologies identified gene drive mosquitoes as a priority technology for malaria elimination. The first field trials are expected in 5–10 years in Uganda, Mali or Burkina Faso. In preparation, regional and international actors are developing risk governance guidelines which will delineate the framework for identifying and evaluating risks. Scientists and bioethicists have called for African stakeholder involvement in these developments, arguing the knowledge and perspectives of those people living in malaria-afflicted countries is currently missing. However, few African stakeholders have been involved to date, leaving a knowledge gap about the local social-cultural as well as ecological context in which gene drive mosquitoes will be tested and deployed. This study investigates and analyses Ugandan stakeholders’ hopes and concerns about gene drive mosquitoes for malaria control and explores the new directions needed for risk governance.
Lessons from Drosophila: Engineering Genetic Sexing Strains with Temperature-Sensitive Lethality for Sterile Insect Technique Applications
T. N. M. Nguyen, A. Choo and S. W. Baxter, Insects, 12. 2021-03-13 16:03:00.Some of the most successful Genetic Sexing Strains (GSS) reared and released for SIT control were developed for Mediterranean fruit fly (Medfly), Ceratitis capitata, and carry a temperature sensitive lethal (tsl) mutation that eliminates female but not male embryos when heat treated. The Medfly tsl mutation was generated by random mutagenesis and the genetic mechanism causing this valuable heat sensitive phenotype remains unknown. Conditional temperature sensitive lethal mutations have also been developed using random mutagenesis in the insect model, Drosophila melanogaster, and were used for some of the founding genetic research published in the fields of neuro- and developmental biology. Here we review mutations in select D. melanogaster genes shibire, Notch, RNA polymerase II 215kDa, pale, transformer-2, Dsor1 and CK2α that cause temperature sensitive phenotypes. Precise introduction of orthologous point mutations in pest insect species with CRISPR/Cas9 genome editing technology holds potential to establish GSSs with embryonic lethality to improve and advance SIT pest control.
Current Effector and Gene-Drive Developments to Engineer Arbovirus-Resistant Aedes aegypti (Diptera: Culicidae) for a Sustainable Population Replacement Strategy in the Field
16596W. R. Reid, K. E. Olson and A. W. E. Franz, J Med Entomol, 2021-03-12 20:35:28.
Conventional mosquito control efforts based on insecticide treatments and/or the use of bednets and window curtains are currently insufficient to reduce arbovirus prevalence in affected regions. Novel, genetic strategies that are being developed involve the genetic manipulation of mosquitoes for population reduction and population replacement purposes. Population replacement aims at replacing arbovirus-susceptible wild-type mosquitoes in a target region with those that carry a laboratory-engineered antiviral effector to interrupt arboviral transmission in the field.
When More is Less: Mosquito Population Suppression Using Sterile, Incompatible and Genetically Modified Male Mosquitoes
18708S. L. Dobson, Journal of Medical Entomology, 58:1980-1986. 2021-03-11 13:50:08.
The current review of the Sterile Insect Technique (SIT) is motivated by new technologies and the recent renaissance of male release field trials, which is driving an evolution in mosquito control and regulation. Practitioners that are releasing male mosquitoes would do well to learn from past successes and failures, including political and public engagement complications. With examples that include nuanced integrations of the different technologies, e.g., combinations of Wolbachia and irradiation, it is critical that scientists understand and communicate accurately about the technologies, including their evolving management by different regulatory agencies in the USA. Some male release approaches are considered ‘pesticides’ and regulated by federal and state agencies, while other male release approaches are unregulated. It is important to consider how the new technologies fit with the more ‘traditional’ chemical applications of adulticides and larvicides. The economics of male release programs are substantially different from traditional control costs, which can be a challenge to their adoption by abatement districts. However, there is substantial need to overcome these complications and challenges, because the problem with invasive mosquitoes grows ever worse with factors that include insecticide resistance, globalization and climate change.
femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes
16910E. Krzywinska, L. Ferretti, J. Li, J.-C. Li, C.-H. Chen and J. Krzywinski, Current Biology, 31:1084-1091.e4. 2021-03-08 18:07:47.
Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria.
Sex Determination and Dosage Compensation: femaleless Is the Link in Anopheles Mosquitoes
16908M. Scott, Current Biology, 31:R260-R263. 2021-03-08 18:03:44.
A new study finds that the femaleless gene is essential for sexual development and repression of X-chromosome dosage compensation in the malaria vector Anopheles gambiae. This could provide the basis for a new genetic approach to control this pest.
Experts’ moral views on gene drive technologies: a qualitative interview study
16565N. de Graeff, K. R. Jongsma and A. L. Bredenoord, BMC Medical Ethics, 22:25. 2021-03-08 13:56:59.
Gene drive technologies (GDTs) promote the rapid spread of a particular genetic element within a population of non-human organisms. Potential applications of GDTs include the control of insect vectors, invasive species and agricultural pests. Whether, and if so, under what conditions, GDTs should be deployed is hotly debated. Although broad stances in this debate have been described, the convictions that inform the moral views of the experts shaping these technologies and related policies have not been examined in depth in the academic literature.
Eliminating Mosquitoes with Precision Guided Sterile Males
16563M. Li, T. Yang, M. Bui, S. Gamez, T. Wise, N. P. Kandul, J. Liu, L. Alcantara, H. Lee, J. R. Edula, R. Raban, Y. Zhan, Y. Wang, N. DeBeaubien, J. Chen, H. M. Sanchez C, J. B. Bennett, I. Antoshechkin, C. Montell, J. M. Marshall and O. S. Akbari, bioRxiv, 2021.03.05.434167. 2021-03-06 20:07:26.
Here we develop a molecular genetic control system termed precision guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and eliminate mosquitoes in multigenerational population cages. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.
