All life on earth must maintain the integrity of their genomes in order to survive. Mosquitoes are no exception, and the choice of methods used can influence genome structure, mutation rates, gene duplication and most recently, the effectiveness of gene editing and gene drive technologies. Ae. aegypti typically employs end-joining based repair machinery in place of machinery that relies on sequence homology from ectopic sources. As a result, targeted indel generation in Ae. aegypti using CRISPR/Cas9 based gene editing is highly efficient, while rates of targeted gene knock-in are substantially lower. However, some of the most promising gene drive strategies to achieve population replacement or reduction rely upon homology-based repair processes for their activity, with even a small amount of end-joining repair capable of generating drive-resistant alleles that can slow or stop gene drive efforts. Projects in my lab aim to determine genetic factors in the mosquito that are responsible for the choice and execution of these different forms of repair, and on using that knowledge to influence repair choice. In particular, we are pursuing strategies to increase the efficiency of inserting genetic material into the mosquito genome in a precise manner, as well as developing technologies to program the removal of transgenic sequences.
Image credit: Zapletal, J., Najmitabrizi, N., Erraguntla, M., Lawley, M.A., Myles, K.M., and Adelman, Z. N. (2020) Making gene drive biodegradable. Phil. Trans. R. Soc. B 376: 20190804.