The drive allele is then copied into the cleaved site during homology-directed repair, converting heterozygotes for the drive allele into homozygotes in their germline. These constructs work by cleaving a wild-type allele at a predetermined target site. Such suppression-type drives have been touted as potential control strategies for disease vectors, invasive species, or agricultural pests 1, 2, 3, 5.ĬRISPR-based homing drives promise a flexible gene drive mechanism for both population modification and suppression, and such systems have now been demonstrated in a variety of organisms, including yeast 8, 9, 10, 11, flies 12, 13, 14, 15, 16, 17, 18, mosquitoes 19, 20, 21, and mice 22. Gene drives may also be used for the direct suppression of a population, for example by targeting an essential but haplosufficient gene. These systems could be used for population modification by carrying a payload allele engineered for a particular purpose, such as a transgene that reduces the capacity for malaria transmission in mosquitoes 1, 2, 3, 5.

Gene drives have the potential to rapidly spread through a population by biasing inheritance in their favor 1, 2, 3, 4, 5, 6, 7.

Our results suggest that TARE drives constitute promising candidates for the development of effective, flexible, and regionally confinable drives for population modification. 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. We demonstrate a TARE drive in Drosophila with 88-95% transmission by female heterozygotes. Modeling shows that such drives will have threshold-dependent invasion dynamics, spreading only when introduced above a fitness-dependent frequency. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target. Here, we introduce the Toxin-Antidote Recessive Embryo (TARE) drive. In addition, they are expected to be highly invasive.

However, such drives face a major obstacle in the form of resistance against the drive. Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population.

What is antidote