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Several gene drive systems have been proposed and a few potential candidate strains have already been developed in the laboratory for the control of several organisms, including invasive rodents 5, agricultural pests 6, 7 and disease vectors 2, 3, 4, 8, 9. These technologies rely on the release of genetically engineered individuals that can rapidly propagate genetic constructs through wild populations together with the linked genetic modifications (e.g., knockout of sex determination 2 or fertility genes 3) or the introduction of genetic cargos (e.g., pathogen-killing molecules designed to block the development of parasites within the vector 4). The management of vector and pest populations using nuclease-based gene drives is becoming a realistic possibility, particularly after the recent proof-of-principle demonstrations of genetic control technologies based on the broadly applicable CRISPR–Cas nucleases 1. Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes. Here we show engineering and testing of a genetic approach, based on the germline expression of a phage-derived anti-CRISPR protein (AcrIIA4), able to inactivate CRISPR-based gene drives and restore their inheritance to Mendelian rates in the malaria vector Anopheles gambiae. Technologies capable of halting the spread of gene drives may prove highly valuable in controlling, counteracting, and even reverting their effect on individual organisms as well as entire populations. Gene drives can be intended to reduce reproductive capacity of harmful insects or spread anti-pathogen effectors through wild populations, even when these confer fitness disadvantages.

These techniques consist of releasing genetically modified organisms carrying CRISPR-Cas nucleases designed to bias their inheritance and rapidly propagate desired modifications. CRISPR-based gene drives offer promising means to reduce the burden of pests and vector-borne diseases.