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A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae

2015; Nature Portfolio; Volume: 34; Issue: 1 Linguagem: Inglês

10.1038/nbt.3439

1546-1696

Andrew Hammond, Roberto Galizi, Kyros Kyrou, Alekos Simoni, Carla Siniscalchi, Dimitris Katsanos, Matthew O. Gribble, Dean A. Baker, Eric Marois, Steven Russell, Austin Burt, Nikolai Windbichler, Andrea Crisanti, Tony Nolan,

Insect Resistance and Genetics

Development of a CRISPR/Cas9-based gene drive system in Anopheles gambiae, the main vector for the malaria parasite, paves the way for control of this pest insect. Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.