PROJECT SUMMARY
Billions of people are at risk of contracting vector-borne diseases and there are no drugs or vaccines to treat or
prevent the majority of these infections. Therefore, vector control is the primary tool used for vector-borne
disease prevention. This proposal aims to improve the technologies available to conduct functional analysis of
genes in ¿Ae. aegypti¿, a major vector of dengue, Zika, chikungunya and yellow fever. Additionally, these same
tools can be adapted to develop antiviral effectors for genetic population replacement strategies, which could
be a key tool for the sustainable management of vector-borne disease. While the goal of creating functional
analytic tools for mosquitoes is not novel, the proposed RNA guided, RNA targeting endonuclease tools will
likely be a more efficient technology with less off target effects compared to current RNAi screening
technologies. Furthermore, we use these new technologies to develop antiviral effectors for the development
of disease refractory mosquitoes, which will expect to be an efficient alternative to current RNAi-based antiviral
effectors. Therefore, this project will adapt RNA guided, RNA targeting Cas endonucleases to develop
functional transcriptomic tools and novel post-transcriptional and viral RNA silencing strategies in ¿Ae. aegypti¿.
The tools will be first developed in mosquito cells and then transitioned into an ¿in vivo ¿mosquito model.
Comparative analysis of the efficiency of RNA guided, RNA targeting Cas endonuclease tools, RNAi and Cas9
functional “omics” tools will also be conducted to determine the most robust RNA silencing and functional
genomic analytical strategies. Finally, these tools will be designed to target viral RNA in mosquito cells and in
the whole organism. In the end, we will develop a functional transcriptomics tool that will facilitate the
characterization of ¿Ae. aegypti ¿genes as well as the development of novel antiviral effectors.