Self-limiting population suppression gene drive in the West Nile vector mosquito, Culex quinquefasciatus

Abstract Culex mosquitoes transmit major pathogens including West Nile virus, encephalitis, filariasis, and avian malaria, threatening public health, poultry, and ecosystems. We engineered a CRISPR-based population suppression gene drive targeting a conserved exon of the doublesex (dsx) gene. The drive incorporates a recoded dsxM segment to preserve male function while converting genetic females into sterile intersexes, enabling male-biased propagation and removal of fertile females. It achieves super-Mendelian inheritance (~ 71%) and generates partially dominant sterile resistance alleles via end-joining, resulting in intersex phenotypes with reduced fertility and hatchability. Modeling predicts that this RIDD (Release of Insects carrying a Dominant-sterile Drive) system can suppress populations at low intrinsic growth rates and release ratios, outperforming SIT and fs-RIDL strategies in persistence and efficiency, with further gains achievable through improved cleavage rates. This study establishes a self-limiting gene drive framework for Culex suppression, highlightling the potential of targeting conserved sex-determination pathways for sustainable vector control.