Featured Articles

Mark-release-recapture experiment in Burkina Faso demonstrates reduced fitness and dispersal of genetically-modified sterile malaria mosquitoes

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F. A. Yao, A.-A. Millogo, P. S. Epopa, A. North, F. Noulin, K. Dao, M. Drabo, C. Guissou, S. Kekele, M. Namountougou, R. K. Ouedraogo, L. Pare, N. Barry, R. Sanou, H. Wandaogo, R. K. Dabire, A. McKemey, F. Tripet and A. Diabaté,  Nature Communications,  13:796. 2022-02-10 09:11:33.
Every year, malaria kills approximately 405,000 people in Sub-Saharan Africa, most of them children under the age of five years. In many countries, progress in malaria control has been threatened by the rapid spread of resistance to antimalarial drugs and insecticides. Novel genetic mosquito control approaches could play an important role in future integrated malaria control strategies. In July 2019, the Target Malaria consortium proceeded with the first release of hemizygous genetically-modified (GM) sterile and non-transgenic sibling males of the malaria mosquito Anopheles coluzzii in Burkina Faso. This study aimed to determine the potential fitness cost associated to the transgene and gather important information related to the dynamic of transgene-carrying mosquitoes, crucial for next development steps. Bayesian estimations confirmed that GM males had lower survival and were less mobile than their wild type (WT) siblings. The estimated male population size in Bana village, at the time of the release was 28,000 - 37,000. These results provide unique information about the fitness and behaviour of released GM males that will inform future releases of more effective strains of the A. gambiae complex.

A flavivirus-inducible gene expression system that modulates broad-spectrum antiviral activity against dengue and Zika viruses

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S.-C. Weng, Y.-X. Zhou and S.-H. Shiao,  Insect Biochemistry and Molecular Biology,  142:103723. 2022-02-02 11:40:32.
Incidence of dengue virus (DENV) and Zika virus (ZIKV), two mosquito-borne flaviviruses, is increasing in large parts of the world. Vaccination and medication for these diseases are unsatisfactory. Here, we developed a novel antiviral approach, using a virus-inducible gene expression system, to block virus replication and transmission. Constructs containing the smallest replication units of dengue virus serotype 2 (DENV2) with negative-stranded DENV2 artificial genomes and genes of interest were established in an Aedes aegypti cell line, resulting in expression of target genes after DENV2 infection. Green fluorescent protein (GFP) assays confirmed the system was virus-inducible. When we used one of two apoptosis-related genes, A. aegypti michelob_x (AaMx) and inhibitor of apoptosis (IAP)-antagonist michelob_x-like protein (AaIMP) instead of GFP, the production of viral RNA and proteins were inhibited for all five viruses tested (DENV1–4 and ZIKV), and effector caspase activity was induced. The system thus inhibited the production of infectious virus particles in vitro, and in mosquitoes it did so after DENV2 infection. This is a novel broad-spectrum antiviral approach using a flavivirus-inducible gene-expression system, which could lead to new avenues for mosquito-borne disease control.

Self-limiting fall armyworm: a new approach in development for sustainable crop protection and resistance management

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C. E. Reavey, A. S. Walker, S. P. Joyce, L. Broom, A. Willse, K. Ercit, M. Poletto, Z. H. Barnes, T. Marubbi, B. J. Troczka, D. Treanor, K. Beadle, B. Granville, V. de Mello, J. Teal, E. Sulston, A. Ashton, L. Akilan, N. Naish, O. Stevens, N. Humphreys-Jo,  BMC Biotechnology,  22:5. 2022-01-27 09:04:56.
Here, we describe the first germline transformation of the fall armyworm and the development of a genetically engineered male-selecting self-limiting strain, OX5382G, which exhibits complete female mortality in the absence of an additive in the larval diet. Laboratory experiments showed that males of this strain are competitive against wild-type males for copulations with wild-type females, and that the OX5382G self-limiting transgene declines rapidly to extinction in closed populations following the cessation of OX5382G male releases. Population models simulating the release of OX5382G males in tandem with Bt crops and non-Bt ‘refuge’ crops show that OX5382G releases can suppress fall armyworm populations and delay the spread of resistance to insecticidal proteins

Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species

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G. Rašić, N. F. Lobo, E. H. Jeffrey Gutiérrez, C. H. Sánchez and J. M. Marshall,  Frontiers in Genetics,  12:780327. 2022-01-25 09:18:49.
As gene drive mosquito projects advance from contained laboratory testing to semi-field testing and small-scale field trials, there is a need to assess monitoring requirements to: i) assist with the effective introduction of the gene drive system at field sites, and ii) detect unintended spread of gene drive mosquitoes beyond trial sites, or resistance mechanisms and non-functional effector genes that spread within trial and intervention sites. This is of particular importance for non-localized gene drive projects, as the potential scale of intervention means that monitoring is expected to be more costly than research, development and deployment. Regarding monitoring needs for population replacement systems, lessons may be learned from experiences with Wolbachia-infected mosquitoes, and for population suppression systems, from experiences with releases of genetically sterile male mosquitoes. For population suppression systems, assessing monitoring requirements for tracking population size and detecting rare resistant alleles are priorities, while for population replacement systems, allele frequencies must be tracked, and pressing concerns include detection of gene drive alleles with non-functional effector genes, and resistance of pathogens to functional effector genes. For spread to unintended areas, open questions relate to the optimal density and placement of traps and frequency of sampling in order to detect gene drive alleles, drive-resistant alleles or non-functional effector genes while they can still be effectively managed. Invasive species management programs face similar questions, and lessons may be learned from these experiences. We explore these monitoring needs for gene drive mosquito projects progressing through the phases of pre-release, release and post-release.

The Need for a Tiered Registry for US Gene Drive Governance

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K. L. Warmbrod, A. L. Kobokovich, R. West, G. K. Gronvall and M. Montague,  Health Security,  2022-01-10 10:08:26.
A great deal of attention has been focused on the potential risks of gene drives, the kinds of biosafety protections they may require, and how they may be reversed; however, less attention has been paid to the systems that would be useful to have in place in the future, when multiple gene drives may be fielded in multiple species, environments, and countries.4-7 The need for coordinated governance of these technologies will become more pressing as gene drive technologies advance and more drives are created to address other vector-borne diseases like the West Nile virus, agricultural pest management, or invasive species. Gene drives carry different inherent risks compared with other genetically modified organisms (GMOs). Existing governance mechanisms for traditional GMOs are insufficient for oversight of gene drives, which require different systems to assess their usefulness and safety. To address the needs for enhanced oversight, we propose a tiered registry system, similar to the clinical trials databases, which can provide government officials, researchers, biotechnology companies, and the public with useful information about ongoing gene drive research or previously released gene drives. Such a resource would enable scientists to confirm that new gene drives would not interfere with existing drives, provide the public with the information needed to make informed decisions concerning consent for release of gene drives, provide researchers with technical information needed to prevent collisions of independent projects modifying the same organism, and provide regulators with information critical for effective oversight. We propose that the US government should implement such a registry for gene drives in the United States, which does not have a robust gene drive regulatory system in place and is not party to the international treaty most relevant for international gene drive regulation, the Convention on Biological Diversity.8 In this commentary, we describe current efforts to safely regulate gene drive and similar genetic technologies worldwide and how the United States could build a tiered registry database that is specifically designed to regulate such technologies throughout a drive's life cycle.

Facilitating the Conversation: Gene Drive Classification

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J. Overcash and A. Golnar,  Health Security,  2021-12-29 13:09:10.
Gene drives are an emerging technology with tremendous potential to impact public health, agriculture, and conservation. While gene drives can be described simply as selfish genetic elements (natural or engineered) that are inherited at non-Mendelian rates, upon closer inspection, engineered gene drive technology is a complex class of biotechnology that uses a diverse number of genetic features to bias rates of inheritance. As a complex technology, gene drives can be difficult to comprehend, not only for the public and stakeholders, but also to risk assessors, risk managers, and decisionmakers not familiar with gene drive literature. To address this difficulty, we describe a gene drive classification system based on 5 functional characteristics. These characteristics include a gene drive's objective, mechanism, release threshold, range, and persistence. The aggregate of the gene drive's characteristics can be described as the gene drive's architecture. Establishing a classification system to define different gene drive technologies should make them more comprehensible to the public and provide a framework to guide regulatory evaluation and decisionmaking.

Evolution of B Chromosomes: From Dispensable Parasitic Chromosomes to Essential Genomic Players

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M. Johnson Pokorná and R. Reifová,  Frontiers in Genetics,  12:727570. 2021-12-09 12:58:40.
B chromosomes represent additional chromosomes found in many eukaryotic organisms. Their origin is not completely understood but recent genomic studies suggest that they mostly arise through rearrangements and duplications from standard chromosomes. They can occur in single or multiple copies in a cell and are usually present only in a subset of individuals in the population. Because B chromosomes frequently show unstable inheritance, their maintenance in a population is often associated with meiotic drive or other mechanisms that increase the probability of their transmission to the next generation. For all these reasons, B chromosomes have been commonly considered to be nonessential, selfish, parasitic elements. Although it was originally believed that B chromosomes had little or no effect on an organism's biology and fitness, a growing number of studies have shown that B chromosomes can play a significant role in processes such as sex determination, pathogenicity and resistance to pathogens. In some cases, B chromosomes became an essential part of the genome, turning into new sex chromosomes or germline-restricted chromosomes with important roles in the organism's fertility. Here, we review such cases of "cellular domestication" of B chromosomes and show that B chromosomes can be important genomic players with significant evolutionary impact.

CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes

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C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, S. K. Mahadevaiah, O. A. Ojarikre, P. J. I. Ellis and J. M. A. Turner,  Nature Communications,  12:6926. 2021-12-03 15:06:30.
Animals are essential genetic tools in scientific research and global resources in agriculture. In both arenas, a single sex is often required in surplus. The ethical and financial burden of producing and culling animals of the undesired sex is considerable. Using the mouse as a model, we develop a synthetic lethal, bicomponent CRISPR-Cas9 strategy that produces male- or female-only litters with one hundred percent efficiency. Strikingly, we observe a degree of litter size compensation relative to control matings, indicating that our system has the potential to increase the yield of the desired sex in comparison to standard breeding designs. The bicomponent system can also be repurposed to generate postnatal sex-specific phenotypes. Our approach, harnessing the technological applications of CRISPR-Cas9, may be applicable to other vertebrate species, and provides strides towards ethical improvements for laboratory research and agriculture.

AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application

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Hendrichs, J. Pereira, R., Vreysen, M. J. B.,  AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application,  2021-11-29 17:04:54.
The concept of area-wide integrated pest management (AW-IPM), in which the total population of a pest in an area is targeted, is central to the effective control of such populations through the integration of genetic, biological and other pest suppression technologies. Insect movement, occurring sometimes over long distances, is generally underestimated. As a consequence, most conventional pest management is implemented as a localized or field-by-field, un-coordinated action against segments of a pest population, not taking in consideration insect movement, resulting very often in an unsustainable spiral of insecticide application and eventual resistance of the pest against the used insecticides. On the other hand, an AW-IPM approach adopts a preventive rather than a reactive strategy, whereby all individuals of the pest population are targeted in time and space and selecting a time when the pest populations are more vulnerable (e.g. during certain times of the year when the population densities are naturally low), requiring in the longer term fewer inputs and resulting in more cost-effective and sustainable pest management. It involves a coordinated effort over often larger areas, including not only agricultural, but also natural and other areas with pest presence. By addressing these sources of reinfestation in the surroundings of the agricultural areas, satisfactory pest control is achieved in the whole area and fewer control actions are required. This new textbook on AW-IPM assembles a series of selected papers that attempts to address various fundamental components of AW-IPM, e.g. the importance of relevant problem-solving research, the need for essential baseline data, the significance of integrating adequate tools for appropriate control strategies, and the value of pilot trials, etc. Of special interest are the numerous papers on pilot and operational programmes that pay special attention to practical problems encountered during the implementation of insect pest control programmes. A significant number of contributions to this book resulted from oral and poster presentations at the Third FAO/IAEA International Conference on “Area-wide Management of Insect Pests: Integrating the Sterile Insect and Related Nuclear and Other Techniques”, which was successfully held from 22-26 May 2017 at the Vienna International Centre, Vienna, Austria. The conference was attended by 360 delegates from 81 countries and six international organization. However, the book contributions were selected beyond the work presented at the conference and a number of experts dealing mainly with action programmes were invited to present their work in this publication

Molecular Mechanisms and Evolutionary Consequences of Spore Killers in Ascomycetes

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S. Zanders and H. Johannesson,  Microbiology and Molecular Biology Reviews,  2021-11-10 22:05:58.
In this review, we examine the fungal spore killers. These are meiotic drive elements that cheat during sexual reproduction to increase their transmission into the next generation. Spore killing has been detected in a number of ascomycete genera, including Podospora, Neurospora, Schizosaccharomyces, Bipolaris, and Fusarium. There have been major recent advances in spore killer research that have increased our understanding of the molecular identity, function, and evolutionary history of the known killers. The spore killers vary in the mechanism by which they kill and are divided into killer-target and poison-antidote drivers. In killer-target systems, the drive locus encodes an element that can be described as a killer, while the target is an allele found tightly linked to the drive locus but on the nondriving haplotype. The poison-antidote drive systems encode both a poison and an antidote element within the drive locus. The key to drive in this system is the restricted distribution of the antidote: only the spores that inherit the drive locus receive the antidote and are rescued from the toxicity of the poison. Spore killers also vary in their genome architecture and can consist of a single gene or multiple linked genes. Due to their ability to distort meiosis, spore killers gain a selective advantage at the gene level that allows them to increase in frequency in a population over time, even if they reduce host fitness, and they may have significant impact on genome architecture and macroevolutionary processes such as speciation.

Containment Practices for Arthropods Modified with Engineered Transgenes Capable of Gene Drive Addendum 1 to the Arthropod Containment Guidelines, Version 3.2

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American Committee of Medical Entomology,  Vector-Borne and Zoonotic Diseases,  2021-10-28 20:19:33.
Responsible conduct of research is a cornerstone of rigorous scientific discovery. Institutional committees, independent advisory panels, and expert steering groups are among the frameworks in academia meant to provide guidance and assurances that research activities do not result in harm to the environment, research staff, or public safety. For research involving arthropods of public health importance, several documents currently exist to guide investigators in methodologies to consider for reducing risks from arthropod escape. However, to date, there has been no standardized set of recommendations on containment practices for arthropods modified with engineered transgenes capable of gene drive. This document is meant to serve as a practical reference to fill that gap. Recommendations outlined here address containment considerations when a risk assessment indicates a possibility of establishment of a new arthropod vector species or genetically modified arthropods in the local environment.

Releasing incompatible males drives strong suppression across populations of wild and Wolbachiat-carrying Aedes aegypti in Australia

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N. W. Beebe, D. Pagendam, B. J. Trewin, A. Boomer, M. Bradford, A. Ford, C. Liddington, A. Bondarenco, P. J. De Barro, J. Gilchrist, C. Paton, K. M. Staunton, B. Johnson, A. J. Maynard, G. J. Devine, L. E. Hugo, G. Rasic, H. Cook, P. Massaro, N. Snoad, J.,  Proceedings of the National Academy of Sciences,  118:e2106828118. 2021-10-05 11:33:10.
Through replicated treatment and control experiments in northern Australia, regular releases of Aedes aegypti males infected with a Wolbachia from Aedes albopictus was shown to drive strong population suppression in mosaic populations of wild-type (no Wolbachia) and wMel-Wolbachia–carrying Ae. aegypti. In a demonstration of bidirectional incompatibility between different Wolbachia strains in the field, we also demonstrate that one season’s suppression experiment can also show an ongoing effect into the following season.Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative venture with the “Debug” Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector Aedes aegypti in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of Ae. aegypti carrying Wolbachia wAlbB from Aedes albopictus with a local strain, we generated a wAlbB2-F4 strain incompatible with both the wild-type (no Wolbachia) and wMel-Wolbachia Ae. aegypti now extant in North Queensland. The wAlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult Ae. aegypti early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and wMel-Ae. aegypti confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable

A single mutation weakens symbiont-induced reproductive manipulation through reductions in deubiquitylation efficiency

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J. F. Beckmann, K. Van Vaerenberghe, D. E. Akwa and B. S. Cooper,  Proceedings of the National Academy of Sciences,  118:e2113271118. 2021-09-21 14:01:04.
We show that a single naturally observed mutation weakens CI by reducing deubiquitylation. These discoveries help elucidate the molecular basis of symbiont-induced reproductive manipulations.Animals interact with microbes that affect their performance and fitness, including endosymbionts that reside inside their cells. Maternally transmitted Wolbachia bacteria are the most common known endosymbionts, in large part because of their manipulation of host reproduction. For example, many Wolbachia cause cytoplasmic incompatibility (CI) that reduces host embryonic viability when Wolbachia-modified sperm fertilize uninfected eggs. Operons termed cifs control CI, and a single factor (cifA) rescues it, providing Wolbachia-infected females a fitness advantage. Despite CI’s prevalence in nature, theory indicates that natural selection does not act to maintain CI, which varies widely in strength. Here, we investigate the genetic and functional basis of CI-strength variation observed among sister Wolbachia that infect Drosophila melanogaster subgroup hosts. We cloned, Sanger sequenced, and expressed cif repertoires from weak CI–causing wYak in Drosophila yakuba, revealing mutations suspected to weaken CI relative to model wMel in D. melanogaster. A single valine-to-leucine mutation within the deubiquitylating (DUB) domain of the wYak cifB homolog (cidB) ablates a CI-like phenotype in yeast. The same mutation reduces both DUB efficiency in vitro and transgenic CI strength in the fly, each by about twofold. Our results map hypomorphic transgenic CI to reduced DUB activity and indicate that deubiquitylation is central to CI induction in cid systems. We also characterize effects of other genetic variation distinguishing wMel-like cifs. Importantly, CI strength determines Wolbachia prevalence in natural systems and directly influences the efficacy of Wolbachia biocontrol strategies in transinfected mosquito systems. These approaches rely on strong CI to reduce human disease.All study data are included in the article and/or supporting information.

Suppressing mosquito populations with precision guided sterile males

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M. 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. Sánchez C, J. B. Bennett, I. Antoshechkin, C. Montell, J. M. Marshall and O. S. Akbari,  Nature Communications,  12:5374. 2021-09-10 14:42:45.
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, 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 flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. 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.

Unravelling the mystery of female meiotic drive: where we are

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F. E. Clark and T. Akera,  Open Biol,  11:210074. 2021-09-02 13:30:18.
Female meiotic drive is the phenomenon where a selfish genetic element alters chromosome segregation during female meiosis to segregate to the egg and transmit to the next generation more frequently than Mendelian expectation. While several examples of female meiotic drive have been known for many decades, a molecular understanding of the underlying mechanisms has been elusive. Recent advances in this area in several model species prompts a comparative re-examination of these drive systems. In this review, we compare female meiotic drive of several animal and plant species, highlighting pertinent similarities.

The international governance of gene drive organisms

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F. Rabitz,  Environmental Politics,  2021-08-29 13:07:16.
Gene Drive Organisms (GDOs) are a proposed biotechnological intervention that might generate significant benefits for the conservation and sustainable use of biological diversity while also raising critical biosafety issues. Despite their inevitable transboundary effects, their implications for international institutions remain undertheorized. This text develops a theoretical analysis of international GDO governance. First, it elaborates the problem-structural characteristics of GDOs that turn them into a novel and distinct governance challenge, focusing on leverage, cost-benefit distributions, irreversibility, as well as uncertainty and unpredictability. Second, it derives the implications of problem structure for institutional design by focusing on pre-release risk assessment and authorization, as well as post-release monitoring and liability. Third, it uses these institutional implications for benchmarking the Cartagena Protocol on Biosafety, the focal point in international biotechnology regulation, for effective GDO governance. The text concludes that institutional reforms are required for folding GDOs into international biodiversity policy.

A common gene drive language eases regulatory process and eco-evolutionary extensions

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P. Verma, R. G. Reeves and C. S. Gokhale,  BMC Ecology and Evolution,  21:156. 2021-08-09 14:36:22.
Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The extraordinary diversity of plausible drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties, particularly where multiple approaches are combined. The sheer number of published manuscripts in this field, experimental and theoretical, the numerous techniques resulting in an explosion in the gene drive vocabulary hinder the regulators’ point of view. We address this concern by defining a simplified parameter based language of synthetic drives. Employing the classical population dynamics approach, we show that different drive construct (replacement) mechanisms can be condensed and evaluated on an equal footing even where they incorporate multiple replacement drives approaches. Using a common language, it is then possible to compare various model properties, a task desired by regulators and policymakers. The generalization allows us to extend the study of the invasion dynamics of replacement drives analytically and, in a spatial setting, the resilience of the released drive constructs. The derived framework is available as a standalone tool. Besides comparing available drive constructs, our tool is also useful for educational purpose. Users can also explore the evolutionary dynamics of future hypothetical combination drive scenarios. Thus, our results appraise the properties and robustness of drives and provide an intuitive and objective way for risk assessment, informing policies, and enhancing public engagement with proposed and future gene drive approaches.

The Promise of Genetics and Genomics for Improving Invasive Mammal Management on Islands

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B. T. Burgess, R. L. Irvine, G. R. Howald and M. A. Russello,  Frontiers in Ecology and Evolution,  9. 2021-08-03 13:21:15.
Invasive species are major contributors to global biodiversity decline. Invasive mammalian species (IMS), in particular, have profound negative effects in island systems that contain disproportionally high levels of species richness and endemism. The eradication and control of IMS have become important conservation tools for managing species invasions on islands, yet these management operations are often subject to failure due to knowledge gaps surrounding species- and system-specific characteristics, including invasion pathways and contemporary migration patterns. Here, we synthesize the literature on ways in which genetic and genomic tools have effectively informed IMS management on islands, specifically associated with the development and modification of biosecurity protocols, and the design and implementation of eradication and control programs. In spite of their demonstrated utility, we then explore the challenges that are preventing genetics and genomics from being implemented more frequently in IMS management operations from both academic and non-academic perspectives, and suggest possible solutions for breaking down these barriers. Finally, we discuss the potential application of genome editing to the future management of invasive species on islands, including the current state of the field and why islands may be effective targets for this emerging technology.

Risk management recommendations for environmental releases of gene drive modified insects

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Y. Devos, J. D. Mumford, M. B. Bonsall, D. C. M. Glandorf and H. D. Quemada,  Biotechnology Advances,  2021-07-25 13:02:06.
The ability to engineer gene drives (genetic elements that bias their own inheritance) has sparked enthusiasm and concerns. Engineered gene drives could potentially be used to address long-standing challenges in the control of insect disease vectors, agricultural pests and invasive species, or help to rescue endangered species. However, risk concerns and uncertainty associated with potential environmental release of gene drive modified insects (GDMIs) have led some stakeholders to call for a global moratorium on such releases or the application of other strict precautionary measures to mitigate perceived risk assessment and risk management challenges. Instead, we provide recommendations that may help to improve the relevance of risk assessment and risk management frameworks for environmental releases of GDMIs. These recommendations include: (1) developing additional and more practical risk assessment guidance to ensure appropriate levels of safety; (2) making policy goals and regulatory decision-making criteria operational for use in risk assessment so that what constitutes harm is clearly defined; (3) ensuring a more dynamic interplay between risk assessment and risk management to manage uncertainty through closely interlinked pre-release modelling and post-release monitoring; (4) considering potential risks against potential benefits, and comparing them with those of alternative actions to account for a wider (management) context; and (5) implementing a modular, phased approach to authorisations for incremental acceptance and management of risks and uncertainty. Along with providing stakeholder engagement opportunities in the risk analysis process, the recommendations proposed may enable risk managers to make choices that are more proportionate and adaptive to potential risks, uncertainty and benefits of GDMI applications, and socially robust.

Combating mosquito-borne diseases using genetic control technologies

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G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari,  Nature Communications,  12:4388. 2021-07-19 13:06:45.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito control strategies including gene drives have been developed to address these problems, both requiring the release of modified mosquitoes into the environment. Here, we review the latest developments, notable similarities, and critical distinctions between these promising technologies and discuss their future applications for mosquito-borne disease control.

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