A toxin-antidote CRISPR gene drive system for regional population modification

Jackson Champer (), Esther Lee, Emily Yang, Chen Liu, Andrew G. Clark and Philipp W. Messer ()
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Jackson Champer: Cornell University
Esther Lee: Cornell University
Emily Yang: Cornell University
Chen Liu: Cornell University
Andrew G. Clark: Cornell University
Philipp W. Messer: Cornell University

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. Here, we introduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target. Modeling shows that such drives will have threshold-dependent invasion dynamics, spreading only when introduced above a fitness-dependent frequency. We demonstrate a TARE drive in Drosophila with 88-95% transmission by female heterozygotes. This drive was able to spread through a large cage population in just six generations following introduction at 24% frequency without any apparent evolution of resistance. Our results suggest that TARE drives constitute promising candidates for the development of effective, flexible, and regionally confinable drives for population modification.

Date: 2020
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DOI: 10.1038/s41467-020-14960-3

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