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A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression

Chrysanthi Taxiarchi, Andrea Beaghton, Nayomi Illansinhage Don, Kyros Kyrou, Matthew Gribble, Dammy Shittu, Scott P. Collins, Chase L. Beisel, Roberto Galizi () and Andrea Crisanti ()
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Chrysanthi Taxiarchi: Imperial College London
Andrea Beaghton: Imperial College London
Nayomi Illansinhage Don: Imperial College London
Kyros Kyrou: Imperial College London
Matthew Gribble: Imperial College London
Dammy Shittu: Imperial College London
Scott P. Collins: North Carolina State University
Chase L. Beisel: North Carolina State University
Roberto Galizi: Keele University
Andrea Crisanti: Imperial College London

Nature Communications, 2021, vol. 12, issue 1, 1-8

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

Date: 2021
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DOI: 10.1038/s41467-021-24214-5

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