Mosquito-based malaria control through genetic, microbial and immunological innovations.

Malaria remains a major global health challenge, causing approximately 600,000 deaths annually despite decades of progress using insecticide-based and drug-based interventions. These core tools are increasingly compromised by widespread insecticide resistance in mosquitoes, drug resistance in parasites, adaptive vector behaviours and the lack of highly effective vaccines, together with logistical and sustainability constraints. Complementary strategies, including larval source management, environmental modification and novel insecticide formulations, also require sustained investment and strong community engagement. Novel Plasmodium transmission-blocking and Anopheles population-suppressing technologies, based on transgenic gene drives, natural and engineered microorganisms, and transmission-blocking vaccines and drugs, have the potential to redefine malaria control by providing parallel, sustainable, mosquito-targeted interventions. In this Review, we synthesize scientific advances underpinning these innovations, identify key knowledge gaps and discuss the science-based safeguards necessary for the responsible implementation of these malaria control strategies.