Harnessing the highly adaptable barnase-barstar system for genetic biocontrol of Aedes aegypti

Toxin-antidote pairs can be used in gene drive systems, providing powerful means to modify mosquito populations. Here we use the toxin-antidote pair, barnase and barstar, originally identified in Bacillus amyloliquefaciens, due to their high binding affinity, small size and lack of need for cofactors. In Ae. aegypti cell culture, we find that barnase can kill and barstar can rescue the effect. Ubiquitous expression of barnase in transgenic mosquitoes results in up to 100% lethality. Tissue specific expression results in flightless or reduced fertility in females and this could be partially rescued by ubiquitous expression of barstar likely due to insufficient expression of barstar in affected tissues. In conclusion, we show barnase-barstar to be a highly adaptable toxin-antidote pair, providing a basis for developing toxin-antidote gene drive systems.