Bernardini, F.; Strampelli, A.; Willis, K.; Gulliford, H. R.; Gribble, M.; Fasulo, B.; Burt, A.; Crisanti, A.

The use of insecticides and antimalarial drugs has been crucial in reducing the mortality and morbidity associated with malaria. However, since 2015, several challenges, including the development of resistance to these insecticides and treatments and changes in mosquito behaviour, have hindered the progress in fighting the disease. As a result, there is a pressing need for new tools to control malaria, including the potential use of genetically modified mosquitoes (GMMs) in the field. Various genetic strategies for vector control are currently being explored, ranging from self-sustaining GMMs with unrestricted geographic and temporal spread to self-limiting alternatives. Here, we propose a self-limiting gene drive strategy called Male Drive Female Sterile (MDFS) targeting Anopheles gambiae, a major malaria vector. The MDFS genetic construct causes dominant sterility in females, while transgenic males remain fertile, allowing them to transmit the female sterility trait at super-Mendelian rates. Laboratory studies have shown that repeated releases of MDFS can lead to the elimination of caged mosquito populations. Based on these findings, modelling suggests that MDFS could be a highly effective and self-limiting strategy for suppressing wild malaria mosquito populations.