2018
DOI: 10.1101/356998
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Integral Gene Drives: an “operating system” for population replacement

Abstract: 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 chal… Show more

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Cited by 3 publications
(3 citation statements)
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“…Transgenes, or alleles of endogenous loci, can be linked with a genetic element conferring drive, and this can promote their spread. A number of approaches to spreading traits through populations (population replacement/alteration/modification) in ways that are self-sustaining, by linking them with genetic elements that mediate drive, have been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) . Several of these, Medea (9,23) , UD mel (15) , engineered translocations (24) , and ClvR ( Cleave and Rescue ) selfish genetic elements (25) , have been implemented and shown to spread to transgene fixation in otherwise wildtype Drosophila .…”
Section: Introductionmentioning
confidence: 99%
“…Transgenes, or alleles of endogenous loci, can be linked with a genetic element conferring drive, and this can promote their spread. A number of approaches to spreading traits through populations (population replacement/alteration/modification) in ways that are self-sustaining, by linking them with genetic elements that mediate drive, have been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) . Several of these, Medea (9,23) , UD mel (15) , engineered translocations (24) , and ClvR ( Cleave and Rescue ) selfish genetic elements (25) , have been implemented and shown to spread to transgene fixation in otherwise wildtype Drosophila .…”
Section: Introductionmentioning
confidence: 99%
“…Lastly, regulatory complexity poses an additional challenge for GD releases. For addressing these challenges, a strategy for the design, phased testing and roll‐out of transmission‐blocking GDs was presented: The construction of minimal, genetically simple GD components out of mosquito genes as well as the molecular separation of the drive and effector functions allows the testing of these in the absence of a full GD . Therefore, a cargo gene could be driven non‐autonomously along with the drive component, where the cargo interferes with pathogen transmission.…”
Section: Applications Of Gene Drivesmentioning
confidence: 99%
“…Previous models have explored how variation in pairs of variables can change either the outcome (Dhole et al 2018;Rode et al 2019) or the internal dynamics (Unckless et al 2015;Dhole et al 2020) of a gene drive. However, many of the features affecting a gene drive vary continuously, potentially interacting with each other to greatly complicate the outcome predictability (Nash et al 2018;Frieß et al 2023). Understanding how the many variables affecting a gene drive influence its fate thus requires their simultaneous testing over a continuous range of values.…”
Section: Introductionmentioning
confidence: 99%