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

PLoS Genet. 2022 Jun 2;18(6):e1010244. doi: 10.1371/journal.pgen.1010244. eCollection 2022 Jun.

Abstract

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 (zpgD) and characterized its behaviour and resistance profile. We found that zpgD dominantly sterilizes females but can induce efficient drive at other loci when it itself encounters resistance. We combined zpgD with multiple previously characterized non-autonomous payload drives and found that, as zpgD 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles* / genetics
  • Antimalarials*
  • Female
  • Gene Drive Technology* / methods
  • Malaria* / genetics
  • Mosquito Control / methods
  • Mosquito Vectors / genetics

Substances

  • Antimalarials

Grants and funding

This work was supported by a Bill and Melinda Gates Foundation grant (OPP1158151) to GKC and NW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.