Researchers report a next-generation gene drive system that could aid the development of strategies to control malaria transmission by mosquitoes. Gene drives aimed at preventing the transmission of parasites by disease vectors must meet stringent technical criteria before field use, including parameters tied to efficiency, specificity, and effects on the fitness of drive-bearing vectors. Anthony James and colleagues report a genetically engineered strain of malaria-transmitting Anopheles gambiae mosquitoes carrying a Cas9/guide RNA-based gene drive. The drive could facilitate the development of future mosquito strains that can be field-tested for malaria mosquito population control. The drive-bearing strain, AgNosCd-1, targets the mosquito's cardinal gene, which encodes an enzyme involved in synthesizing eye color pigment. The drive showed an average efficiency of 96.7% in both sexes, minimal off-target effects in vitro, few adverse effects on the fitness of drive-bearing mosquitoes, and a low frequency of potentially resistant alleles that could counteract it. Importantly, trials in small cages in the lab revealed that a single release of drive-bearing males at 1:1 ratio (AgNosCd-1:wild-type) was sufficient to ensure that every mosquito carried at least one copy of the drive construct within six generations, which represents a period of 6 months and falls within a single annual malaria transmission cycle. Hence, AgNosCd-1 can serve as an efficient vehicle to ferry antiparasite effector genes into mosquitoes. According to the authors, the drive could help speed the development of mosquito strains for future field tests, which would require risk assessment, regulatory oversight, and community engagement.
Article #20-10214: "Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae," by Rebeca Carballar-Lejarazú et al.
MEDIA CONTACT: Anthony James, University of California, Irvine, CA; e-mail: email@example.com
Proceedings of the National Academy of Sciences