Synthetic miRNAs induce dual arboviral-resistance phenotypes in the vector mosquito Aedes aegypti.

Mosquito-borne arboviruses are responsible for recent dengue, chikungunya, and Zika pandemics. The yellow-fever mosquito, Aedes aegypti, plays an important role in the transmission of all three viruses. We developed a miRNA-based approach that results in a dual resistance phenotype in mosquitoes to dengue serotype 3 (DENV-3) and chikungunya (CHIKV) viruses. The target viruses are from two distinct arboviral families and the antiviral mechanism is designed to function through the endogenous miRNA pathway in infected mosquitoes. Challenge experiments showed reductions in viral transmission efficiency of transgenic mosquitoes. Several components of mosquito fitness were examined, and transgenic mosquitoes with the PUb promoter showed minor fitness costs at all developing stages. Further development of these strains with gene editing tools could make them candidates for releases in population replacement strategies for sustainable control of multiple arbovirus diseases.