Nevard Katherine, Ang Joshua X D, Anderson Michelle A E, Gonzalez Estela, Shackleford Lewis, Alphey Luke
Arthropod Genetics, The Pirbright Institute, Pirbright, UK.
The Department of Biology, University of York, York, UK.
Commun Biol. 2025 Aug 4;8(1):1154. doi: 10.1038/s42003-025-08588-6.
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.
毒素-解毒剂对可用于基因驱动系统，为改造蚊子种群提供了有力手段。在此，我们使用最初在解淀粉芽孢杆菌中发现的毒素-解毒剂对barnase和barstar，因其具有高结合亲和力、体积小且无需辅助因子。在埃及伊蚊细胞培养中，我们发现barnase可导致细胞死亡，而barstar可挽救这种效应。在转基因蚊子中普遍表达barnase会导致高达100%的致死率。组织特异性表达会导致雌性蚊子无法飞行或生育力降低，而普遍表达barstar可部分挽救这种情况，这可能是由于受影响组织中barstar表达不足所致。总之，我们证明barnase-barstar是一种高度适应性的毒素-解毒剂对，为开发毒素-解毒剂基因驱动系统奠定了基础。
