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bioRxiv · 10.1101/2025.07.16.665070

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

Feng, X.·Ding, J.·Liu, Y.·Lopez Del Amo, V.·Gantz, V. M.·Chen, X.-x.·Champer, J.·Liu, F.
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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.

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Feng, X., Ding, J., Liu, Y., Lopez Del Amo, V., Gantz, V. M., Chen, X.-x., Champer, J., Liu, F.. 2025-07-19. Self-limiting population suppression gene drive in the West Nile vector mosquito, Culex quinquefasciatus. https://doi.org/10.1101/2025.07.16.665070

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