A toxin-antidote CRISPR gene drive system for regional population modification
A toxin-antidote CRISPR gene drive system for regional population modification
Tags: CRISPR, Gene drive, Gene drive synthetic, Toxin-antidoteJ. Champer, E. Lee, E. Yang, C. Liu, A. G. Clark and P. W. Messer, Nature Communications, 11:1082. 2023.
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.