Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group
               
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James, Stephanie; Collins, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome Amir; Tountas, Karen H.; Touré, Yéya T.

doi:10.4269/ajtmh.18-0083

Cited by 183 publications

(243 citation statements)

References 89 publications

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“…Given the remarkable progress in the gene drive field and potential of gene drives to spread globally, understandably the discussion of the ethics, risks, governance, and the guidance of gene drives in the field have come to the forefront (44,(70)(71)(72). As gene-drive technologies advance and field trials become a necessary step toward understanding the efficacy and behavior of drives in wild populations, it is important that facilities planning and management, infrastructure upgrades, talent development for deployment and monitoring, and public engagement are advanced to support the sustainability of gene drive technologies.…”

Section: Discussionmentioning

confidence: 99%

Development of a Confinable Gene-Drive System in the Human Disease Vector,Aedes aegypti

Li¹,

Yang²,

Kandul³

et al. 2019

Preprint

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Aedes aegypti, the principal mosquito vector for many arboviruses that causes yellow fever, dengue, Zika, and chikungunya, increasingly infects millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has recently sparked significant enthusiasm for the genetic control of mosquito populations, however no such system has been developed in Ae. aegypti. To fill this void and demonstrate efficacy in Ae. aegypti, here we develop several CRISPR-based split-gene drives for use in this vector. With cleavage rates up to 100% and transmission rates as high as 94%, 2 mathematical models predict that these systems could spread anti-pathogen effector genes into wild Ae. aegypti populations in a safe, confinable and reversible manner appropriate for field trials and effective for controlling disease. These findings could expedite the development of effectorlinked gene drives that could safely control wild populations of Ae. aegypti to combat local pathogen transmission. Significance StatementAe. aegypti is a globally distributed arbovirus vector spreading deadly pathogens to millions of people annually. Current control methods are inadequate and therefore new technologies need to be innovated and implemented. With the aim of providing new tools for controlling this pest, here we engineered and tested several split gene drives in this species. These drives functioned at very high efficiency and may provide a tool to fill the void in controlling this vector. Taken together, our results provide compelling path forward for the feasibility of future effector-linked split-drive technologies that can contribute to the safe, sustained control and potentially the elimination of pathogens transmitted by this species.

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Section: Discussionmentioning

confidence: 99%

Development of a Confinable Gene-Drive System in the Human Disease Vector,Aedes aegypti

Li¹,

Yang²,

Kandul³

et al. 2019

Preprint

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“…Strategies to use gene drives in the context of GM insects can be differentiated based on (e.g. Eckhoff et al., ; James et al., ; Scott et al., ): desired outcome: population suppression vs. population replacement, ability of the trait to establish or spread: self‐sustaining vs. self‐limiting drives. …”

Section: Problem Formulation In Practice: Case Studiesmentioning

confidence: 99%

“…As with any technology, however, true understanding of the potential risks to the environment must be informed by a case-specific risk assessment, not a generalised view of the technology (James et al, 2018;Frieß et al, 2019). One specific case example where the use of gene drive mechanisms has been proposed is to target vector mosquitoes in order to reduce or eliminate the spread of malaria (Gantz et al, 2015;Burt et al, 2018;Kyrou et al, 2018).…”

Section: Case Studymentioning

confidence: 99%

Using problem formulation for fit‐for‐purpose pre‐market environmental risk assessments of regulated stressors

Devos

Devlin

Ippolito

et al. 2019

EFS2

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Pre-market/prospective environmental risk assessments (ERAs) contribute to risk analyses performed to facilitate decisions about the market introduction of regulated stressors. Robust ERAs begin with an explicit problem formulation, which involves among other steps: (1) formally devising plausible pathways to harm that describe how the deployment of a regulated stressor could be harmful; (2) formulating risk hypotheses about the likelihood and severity of such events; (3) identifying the information that will be useful to test the risk hypotheses; and (4) developing a plan to acquire new data for hypothesis testing should tests with existing information be insufficient for decision-making. Here, we apply problem formulation to the assessment of possible adverse effects of RNA interference-based insecticidal genetically modified (GM) plants, GM growth hormone coho salmon, gene drive-modified mosquitoes and classical biological weed control agents on non-target organisms in a prospective manner, and of neonicotinoid insecticides on bees in a retrospective manner. In addition, specific considerations for the problem formulation for the ERA of nanomaterials and for landscape-scale population-level ERAs are given. We argue that applying problem formulation to ERA maximises the usefulness of ERA studies for decision-making, through an iterative process, because: (1) harm is defined explicitly from the start; (2) the construction of risk hypotheses is guided by policy rather than an exhaustive attempt to address any possible differences; (3) existing information is used effectively; (4) new data are collected with a clear purpose; (5) risk is characterised against well-defined criteria of hypothesis corroboration or falsification; and (6) risk assessment conclusions can be communicated clearly. However, problem formulation is still often hindered by the absence of clear policy goals and decision-making criteria (e.g. definition of protection goals and what constitutes harm) that are needed to guide the interpretation of scientific information. We therefore advocate further dialogue between risk assessors and risk managers to clarify how ERAs can address policy goals and decision-making criteria. Ideally, this dialogue should take place for all classes of regulated stressors, as this can promote alignment and consistency on the desired level of protection and maximum tolerable impacts across regulated stressors.

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“…The scientific working group on a pathway to deployment of gene drive mosquitoes for elimination of Malaria in Sub-Saharan Africa (James et al 2018) recommends the use of fluorescent markers to track gene drive constructs pre and post-deployment. However, gene drives can decouple from genetically-linked fluorescent marker genes within a single generation of homing, potentially giving rise to type II errors during monitoring, arguably the most crucial error as it would suggest the absence of constructs in populations or regions in which active gene drives are in-fact propagating.…”

Section: Developing Igd Traitsmentioning

confidence: 99%

Integral Gene Drives: an “operating system” for population replacement

Nash

Urdaneta

Beaghton

et al. 2018

Preprint

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First generation CRISPR-based gene drives have now been tested in the laboratory in a number of organisms including malaria vector mosquitoes. A number of challenges for their use in the area-wide genetic control of vector-borne disease have been identified. These include the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and the practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. To address these challenges, we have evaluated the concept of Integral Gene Drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including both the drive and the anti-pathogen effector elements directly embedded within endogenous genes -an arrangement which we refer to as gene "hijacking". This design would allow autonomous and non-autonomous IGD traits and strains to be generated, tested, optimized, regulated and imported independently. We performed quantitative modelling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population while hedging drive over multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target-site variation. IGD thus has the potential to yield more durable and flexible population replacement traits.

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Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group †

Cited by 183 publications

References 89 publications

Development of a Confinable Gene-Drive System in the Human Disease Vector,Aedes aegypti

Development of a Confinable Gene-Drive System in the Human Disease Vector,Aedes aegypti

Using problem formulation for fit‐for‐purpose pre‐market environmental risk assessments of regulated stressors

Integral Gene Drives: an “operating system” for population replacement

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