Vector-borne diseases pose a significant global health burden.
Current strategies to control mosquitoes and the viral diseases they spread rely primarily on the use of insecticides. These measures can have significant adverse effects on local ecology, and mosquitoes are becoming increasingly resistant. Next generation biocontrol tools, such as genome engineering, offer an environmentally safe, customisable, and scalable option in which to control mosquito populations. To this end, we have established a mosquito population control method whereby viral RNA Expression Activates Poisonous Effector Ribonucleases (REAPER), leading to mosquito death if infected with specific viruses.
Here, we have directly manipulated Aedes aegypti mosquito genome to express Cas13 and guide RNAs targeting chikungunya virus. When a mosquito takes an infected blood meal, guide RNAs binds to viral RNA leading to Cas13-mediated cleavage of essential mosquito RNA. This activation of REAPER essentially senses the presence of specific viruses and can lead to premature mosquito death via non-specific targeting of cellular RNA. This novel technique is the first instance of Cas13 mediated biocontrol developed for disease vectors.
Our results show that after infection with chikungunya virus, REAPER is effective at causing death in infected mosquitoes. At 14 days post blood meal with CHIKV, there is a 30% decrease in mosquito survival compared to controls. Viral load of each infected mosquito was also assessed, and a significant decrease (p=0.004) in the amount of virus present was shown in REAPER mosquitoes.
We show that REAPER is a large step forward in mosquito control to prevent arboviral disease transmission, with future work being performed to translate it into different viral targets and mosquito species. Next generational population control strategies such as shown in this study are an increasingly viable tool that could be deployed during viral outbreaks.