Gene drive as a tool to fight mosquito vector-borne diseases

Mosquito vectors of human disease are still responsible for the death of about 750,000 people annually. Genetic resistance to insecticides is spreading in mosquito populations, new arthropod-borne viral diseases emerge continuously and drugs against malaria stimulate the emergence of drug-resistant parasites. In the fight against mosquito-borne disease, the gene drive technology shows great promise to complement existing vector control methods. Gene drives are transgenic constructs designed to invade populations of a target species, based on the activity of molecular scissors such as the CRISPR/Cas9 system. Gene drive could be deployed either for population suppression, which may cause a loss in biodiversity and ecosystem imbalance, or for genetic modification at the scale of a species. In confined laboratory conditions, the researchers will develop gene drive constructs carrying anti-pathogen molecules to render Anopheles gambiae and Aedes aegypti mosquitoes unable to transmit malaria parasites and viruses (dengue, Zika). The researchers will optimize and test several innovative gene drive approaches, with particular attention to avoid the emergence of drive-refractory mosquitoes: multiplex drives; anti-Plasmodium dual-effect drive; drive-or-die constructs; indirect drives. The researchers will monitor the efficiency of each of these strategies in caged mosquitoes, the possible undesired effects arising from on and off-target mutations induced by the drive, develop “recall strains” able to block the drive, and test the constructs’ propensity for horizontal transfer towards other insect species and microorganisms. Project partners have complementary expertise in Anopheles and Aedes biology, in gene engineering and in mosquito infection assays with human pathogens. The researchers hope it will foster the emergence of alternative approaches to insecticide-based control interventions, which are reaching their limits.

Project details

Genetics and Genomics

Oct 2019 — Oct 2023

$499,445

France