A confinable home-and-rescue gene drive for population modification

Homing-based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification home-and-rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy. Finally, we conduct mathematical modeling comparing HomeR to contemporary gene drive architectures for population modification over wide ranges of fitness costs, transmission rates, and release regimens. HomeR could potentially be adapted to other species, as a means for safe, confinable, modification of wild populations.

Automated summary

Homing-based gene drives are proposed to spread desirable genes throughout populations, but resistant alleles can hinder their invasion. A confinable population modification HomeR drive in Drosophila was engineered to target an essential gene, demonstrating an increase in frequency but limited efficacy due to fitness costs. Mathematical modeling compared HomeR to other gene drive architectures for modifying populations, suggesting potential adaptability to other species.