A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population.

ABSTRACT: Engineered gene drives are being explored as a new strategy in the fight against vector-borne diseases due to their potential for rapidly spreading genetic modifications through a population. However, CRISPR-based homing gene drives proposed for this purpose have faced a major obstacle in the formation of resistance alleles that prevent Cas9 cleavage. Here, we present a homing drive in Drosophila melanogaster that reduces the prevalence of resistance alleles below detectable levels by targeting a haplolethal gene with two guide RNAs (gRNAs) while also providing a rescue allele. Resistance alleles that form by end-joining repair typically disrupt the haplolethal target gene and are thus removed from the population because individuals that carry them are nonviable. We demonstrate that

SUBMITTER: Champer J 

PROVIDER: S-EPMC7533649 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature