A home and rescue gene drive efficiently spreads and persists in populations

Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes into target populations. However, spread of such drives can be hindered by the accumulation of resistance alleles. To overcome this significant obstacle, we engineer an inherently confinable population modification<underline>Home</underline>-and-<underline>R</underline>escue (HomeR) drive inDrosophila melanogasterthat, by creative design, limits the accumulation of such alleles. We demonstrate that HomeR can achieve nearly ∼100% transmission enabling it to spread and persist at genotypic fixation in several multi-generational population cage experiments, underscoring its long term stability and drive potential. Finally, we conduct mathematical modeling determining HomeR can outperform contemporary gene drive architectures for population modification over wide ranges of fitness and transmission rates. Given its straightforward design, HomeR could be universally adapted to a wide range of species.