Development of a confinable gene drive system in the human disease vector Aedes aegypti

TLDR

Aedes aegypti is the main vector for many arboviruses, and rising infection rates and limited efficacy of conventional control methods have spurred interest in novel strategies such as gene drives, which have yet to be developed for this species. The study aims to develop CRISPR‑based split gene drives for Aedes aegypti. The authors constructed several CRISPR‑based split gene drives for this vector. Mathematical models predict that the engineered drives, with up to 100 % cleavage and 94 % transmission, can safely and reversibly spread anti‑pathogen genes into wild Aedes aegypti populations, potentially accelerating the deployment of disease‑control gene drives.

Abstract

Aedes aegypti is the principal mosquito vector for many arboviruses that increasingly infect millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has sparked significant enthusiasm for genetic control of mosquitoes; however, no such system has been developed in Ae. aegypti. To fill this void, here we develop several CRISPR-based split gene drives for use in this vector. With cleavage rates up to 100% and transmission rates as high as 94%, mathematical models predict that these systems could spread anti-pathogen effector genes into wild populations in a safe, confinable and reversible manner appropriate for field trials and effective for controlling disease. These findings could expedite the development of effector-linked gene drives that could safely control wild populations of Ae. aegypti to combat local pathogen transmission.