Genetic approaches to reducing vector competence of Aedes aegypti for chikungunya virus

Dengue, chikungunya and other arboviral diseases impose significant morbidity and mortality. In few cases are licensed drugs or vaccines available. However, the dependence of these viruses on specific mosquito species, combined with advances in mosquito synthetic biology, potentially provides new approaches. We will engineer reduced-vector-competence traits in the major vector mosquito Aedes aegypti, focusing on chikungunya virus, though successful development would be significant for a much wider range of viruses. We will pursue three approaches in parallel (i) to mitigate the risk that one of these ambitious approaches may not fully achieve its design goals; (ii) to provide multiple independent means to interfere with virus transmission, which in combination would greatly reduce the possibility of virus escape mutants. Two of these approaches aim to make mosquito cells more resistant to incoming viruses, (exploiting RNAi and super-infection exclusion mechanisms, respectively), the other aims to kill cells on infection so that they are unable to support virus transmission, using synthetic substrates for virus replicase that will be replicated and expressed following infection. Each of these approaches is inspired by natural anti-virus defence mechanisms and uses components and designs based on our strong collective track record in molecular virology and mosquito synthetic biology.