Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
Weizhe Chen, Jialiang Guo, Yiran Liu, Jackson Champer
Abstract
CRISPR homing gene drives can suppress pest populations by targeting female fertility genes, converting wild-type alleles into drive alleles in the germline of drive heterozygotes. fsRIDL (female-specific Release of Insects carrying a Dominant Lethal) is a self-limiting population suppression strategy involving continual release of transgenic males carrying female lethal alleles. Here, we propose an improved pest suppression system called “Release of Insects carrying a Dominant-sterile Drive” (RIDD), combining performance characteristics of homing drive and fsRIDL. We construct a split RIDD system in Drosophila melanogaster by creating a 3-gRNA drive disrupting the doublesex female exon. Drive alleles bias their inheritance in males, while drive alleles and resistance alleles formed by end-joining cause dominant female sterility. Weekly releases of RIDD males progressively suppressed and eventually eliminated cage populations. Modeling shows that RIDD is substantially stronger than SIT and fsRIDL. RIDD is also self-limiting, potentially allowing targeted population suppression. CRISPR homing gene drives can suppress pest populations by targeting female fertility genes, converting wild-type alleles into drive alleles in the germline of drive heterozygotes. Here the authors demonstrate a genetic pest suppression system based on dominant female-sterile doublesex alleles and show that releases of transgenic males eliminated Drosophila cage populations, with modelling showing improved performance compared to similar systems.