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

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

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 b...

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Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; p. 3977
Main Authors: Taxiarchi, Chrysanthi, Beaghton, Andrea, Don, Nayomi Illansinhage, Kyrou, Kyros, Gribble, Matthew, Shittu, Dammy, Collins, Scott P., Beisel, Chase L., Galizi, Roberto, Crisanti, Andrea
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 25-06-2021
Nature Publishing Group
Nature Portfolio
Subjects:
42/35
42/41
42/44
42/70
631/114/2397
631/1647/1511
631/337/4041/3196
631/61/338/552
CRISPR
Culicidae
Deactivation
Genetic code
Genetic modification
Genetically engineered organisms
Genetically modified organisms
Heredity
Humanities and Social Sciences
Infectious diseases
Insects
Malaria
Mosquitoes
multidisciplinary
Nuclease
Pests
Phages
Populations
Proteins
Science
Science (multidisciplinary)
Vector-borne diseases
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Summary: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. Technologies that can halt the spread of gene drives would be highly useful in controlling or reverting their effect. Here the authors use the anti-CRISPR protein AcrIIA4 to inactivate drives in A. gambiae.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24214-5