Malaria-carrying mosquitoes are evolving resistance to the insecticides that have driven recent gains in malaria control, and researchers are now testing whether a genetic tool called a gene drive can be engineered to work in tandem with insecticides to suppress mosquito populations more durably. The problem is that insecticide resistance is spreading, and gene drives—modified CRISPR elements that copy themselves into a mosquito’s genome and disrupt essential genes—are themselves vulnerable to resistance through DNA sequence variation. However, the two control methods attack mosquitoes through completely independent mechanisms. After an insecticide programme kills most mosquitoes, the surviving resistant population has drastically reduced genetic variation, making it more vulnerable to a gene drive that targets the few remaining sequences. Conversely, a gene drive that suppresses a population over the long term could leave any residual mosquitoes newly susceptible to insecticides. If this research succeeds, it could provide a practical strategy for combining traditional and genetic controls to slow or prevent the evolution of resistance—extending the useful life of both bednets and future gene drive releases. The project is at an early, feasibility-testing stage, focusing on a specific gene (vgsc) involved in pyrethroid resistance in African mosquitoes.
View original technical description
Insecticide-based control of mosquitoes has driven the recent huge gains in malaria control, yet insecticide resistance necessitates both new control approaches and ways to combine approaches that drastically reduce the overall likelihood of resistance. Our recent research has demonstrated a new form of genetic control, called gene drive, that can spread a genetic element rapidly in a population and cause its suppression. The gene drive, based on a modified CRISPR element, effectively acts as a very specific form of genomic parasite designed to recognise and disrupt a target sequence in any essential mosquito gene, copying itself in the process. We have shown that gene drives are also subject to resistance, in the form of sequence variation at the target site. Both forms of control show similarities in the dynamics of selection and spread of resistance yet show completely independent modes of action. After initial suppression, insecticide programs can leave a residual resistant population that shows drastically reduced genomic variation ('selective sweeps') making it more susceptible to subsequent control by gene drive. Conversely, it should be possible to engineer gene drives in a way that, after causing long term suppression, any residual population is newly susceptible to insecticide. Target site resistance to pyrethroids is widespread in many African populations of mosquitoes after the extended use of pyrethroid-treated bednets. The genetics of this resistance centre on a particular gene (vgsc) encoding a voltage-gated sodium channel, with many of the key point mutations being known. As a first step we have developed a gene drive that targets the vgsc gene to investigate the feasibility of deliberately affecting this gene's function with a gene drive. Future steps as part of this project will look at the feasibility of targeting resistant versus susceptible alleles of this gene as well as other nearby regions of interest. Sites in these regions are attractive as gene drive targets since many of them show little genetic variation. This project will also investigate the feasibility of targeting these with gene drives that are designed to modify the targeted population through the introduction of 'cargo' genes that encode an effector that affect the mosquito's intrinsic ability to harbour the malaria parasite.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know