Sex distorter male drive for resistance-resilient population control of the human malaria vector Anopheles gambiae

Progress in malaria control has plateaued, prompting the exploration of additional tools. Here, we characterise two germline-specific promoters, spo11 and vasa1, in the malaria vector Anopheles gambiae. These promoters display distinct temporal and spatial expression patterns, making them well-suited for potential applications in CRISPR-based gene drives and sex ratio distortion systems. Leveraging these unique promoter features, we developed a Sex Distorter Male Drive (SDMD) technology that generates a highly male-biased progeny while spreading through super-Mendelian inheritance. This approach greatly simplifies previous genetic construct designs, potentially improving genetic stability and resilience against the development of target site resistance, a major challenge for the efficacy of genetic strategies. Our findings position SDMD as a promising and potentially resistance-resilient tool for the population suppression of Anopheles mosquitoes in malaria-endemic regions.