Engineered gene drives based on a homing mechanism could rapidly spread genetic alterationsthrough a population. However, such drives face a major obstacle in the form ofresistance against the drive. In addition, they are expected to be highly invasive. Here, weintroduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting atarget gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with arecoded version of the target. Modeling shows that such drives will have threshold-dependentinvasion 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 generationsfollowing introduction at 24% frequency without any apparent evolution of resistance. Ourresults suggest that TARE drives constitute promising candidates for the development ofeffective, flexible, and regionally confinable drives for population modification.
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