Components of the Medea gene drive system in a mosquito Aedes aegypti

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Mosquito-borne viral diseases, such as dengue, chikungunya, yellow fever, and Zika continue to be a major international public health problem. Despite control efforts, the numbers of infections are on the increase, which indicates that the existing control strategies, relying on suppression of mosquito vector populations, are not effective. The mosquito Aedes aegypti, responsible for the great majority of infections with these viruses, is difficult to control with the conventional tools. It breeds in various, often cryptic, man-made containers, and their females bite during the day, making their targeting with insecticides very challenging. Moreover, increasing resistance to insecticides in the Ae. aegypti populations further exacerbates the situation. To reduce disease burden, new genetic control strategies have been proposed, aiming at suppression of mosquito populations or at mosquito population modification by releasing engineered mosquitoes incapable of virus transmission. The latter strategies, to be effective, require a mechanism that would allow a rapid spread of the anti-pathogen synthetic constructs through the entire mosquito populations. A gene drive mechanism, called Medea, constructed thus far only in a fruit fly Drosophila melanogaster, has been demonstrated to possess the required invasive properties. Efforts to develop functional Medea element in mosquitoes have not yet met with success, because information about the relevant aspects of mosquito developmental biology is still lacking. In this study, we will focus on elucidation of the key developmental processes occurring in ovaries during egg production and in early Ae. aegypti embryos to identify the most optimal genetic constituents of the Medea element functional in this mosquito species. The identified sequences will be individually validated in transgenic mosquito lines and, subsequently used for the creation of a proof-of-principle functional Medea gene drive in Aedes.