Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae

Author summaryGene drive is a method that allows the genetic modification of entire populations of harmful organisms. Their application to tackle invasive species, agricultural pests or insect disease vectors has been suggested. For example, they could reduce the capacity of malaria mosquitoes to transmit this deadly disease to humans by producing effector molecules inhibiting the development of the Plasmodium parasite in the mosquito vector. We describe a strategy to modularize and test multiple transgenes destined for release, and to introduce only the minimal set of modifications needed into a mosquito population. We show how some elements, once no longer needed, can be made to self-eliminate from populations and we also study how several independent gene drive traits, located in different parts of the genome, can interact and propagate at the level of mosquito cage populations. Gene drives for mosquito population modification are novel tools for malaria control. Strategies to safely test antimalarial effectors in the field are required. Here, we modified the Anopheles gambiae zpg locus to host a CRISPR/Cas9 integral gene drive allele (zpg(D)) and characterized its behaviour and resistance profile. We found that zpg(D) dominantly sterilizes females but can induce efficient drive at other loci when it itself encounters resistance. We combined zpg(D) with multiple previously characterized non-autonomous payload drives and found that, as zpg(D) self-eliminates, it leads to conversion of mosquito cage populations at these loci. Our results demonstrate how self-eliminating drivers could allow safe testing of non-autonomous effector-traits by local population modification. They also suggest that after engendering resistance, gene drives intended for population suppression could nevertheless serve to propagate subsequently released non-autonomous payload genes, allowing modification of vector populations initially targeted for suppression.

Automated summary

The study investigates the application of gene drive technology in mosquito population modification. They use self-eliminating drivers and non-autonomous effector traits to safely test and modify vector populations. The results demonstrate that this approach can propagate non-autonomous payload genes while ensuring population control.