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

Culex quinquefasciatus is a major vector of West Nile virus and other pathogens, yet genetic population suppression tools for this species remain limited. Here, we develop a self-limiting, CRISPR-based suppression gene drive system targeting doublesex, close to the male-determining locus, promoting male transmission. A recoded dsxM sequence converts females into sterile intersexes, preventing population-level spread. The drive achieves super-Mendelian inheritance ( ~ 71%) and generates resistance alleles that are fully or partially dominant female sterile. Single-release cage trials show extended but self-limiting population suppression. Population modeling of this RIDD (Release of Insects carrying a Dominant-sterile Drive) system further indicates that repeated releases can substantially reduce fertile female numbers at low release ratios and intrinsic growth rates, outperforming non-drive strategies under comparable conditions. Together, these results establish a self-limiting suppression gene drive platform for Culex, providing a confined and sustainable framework for vector population control. Culex mosquitoes drive the spread of West Nile virus, yet controlling their populations remains challenging. Here, authors develop a self-limiting CRISPR-based genetic approach that converts female mosquitoes into sterile intersexes, enabling effective and confined population suppression.