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Integral Gene Drives for population replacement

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Title: Integral Gene Drives for population replacement
Authors: Nash, A
Urdaneta Mignini, G
Beaghton, A
Hoermann, A
Papathanos, P
Christophides, G
Windbichler, N
Item Type: Journal Article
Abstract: A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling 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 drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy.
Issue Date: 3-Jan-2019
Date of Acceptance: 21-Nov-2018
URI: http://hdl.handle.net/10044/1/66490
DOI: https://dx.doi.org/10.1242/bio.037762
ISSN: 2046-6390
Publisher: Company of Biologists
Journal / Book Title: Biology Open
Volume: 8
Issue: 1
Copyright Statement: © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Bill & Melinda Gates Foundation
Funder's Grant Number: BB/P000843/1
OPP1158151
Keywords: CRISPR
Gene drive
Genome editing
Population modeling
Population replacement
Publication Status: Published
Appears in Collections:Faculty of Natural Sciences



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