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Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae.


ABSTRACT: A Cas9/guide RNA-based gene drive strain, AgNosCd-1, was developed to deliver antiparasite effector molecules to the malaria vector mosquito, Anopheles gambiae The drive system targets the cardinal gene ortholog producing a red-eye phenotype. Drive can achieve 98 to 100% in both sexes and full introduction was observed in small cage trials within 6 to 10 generations following a single release of gene-drive males. No genetic load resulting from the integrated transgenes impaired drive performance in the trials. Potential drive-resistant target-site alleles arise at a frequency <0.1, and five of the most prevalent polymorphisms in the guide RNA target site in collections of colonized and wild-derived African mosquitoes do not prevent cleavage in vitro by the Cas9/guide RNA complex. Only one predicted off-target site is cleavable in vitro, with negligible deletions observed in vivo. AgNosCd-1 meets key performance criteria of a target product profile and can be a valuable component of a field-ready strain for mosquito population modification to control malaria transmission.

SUBMITTER: Carballar-Lejarazu R 

PROVIDER: S-EPMC7502704 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Next-generation gene drive for population modification of the malaria vector mosquito, <i>Anopheles gambiae</i>.

Carballar-Lejarazú Rebeca R   Ogaugwu Christian C   Tushar Taylor T   Kelsey Adam A   Pham Thai Binh TB   Murphy Jazmin J   Schmidt Hanno H   Lee Yoosook Y   Lanzaro Gregory C GC   James Anthony A AA  

Proceedings of the National Academy of Sciences of the United States of America 20200824 37


A Cas9/guide RNA-based gene drive strain, AgNosCd-1, was developed to deliver antiparasite effector molecules to the malaria vector mosquito, <i>Anopheles gambiae</i> The drive system targets the <i>cardinal</i> gene ortholog producing a red-eye phenotype. Drive can achieve 98 to 100% in both sexes and full introduction was observed in small cage trials within 6 to 10 generations following a single release of gene-drive males. No genetic load resulting from the integrated transgenes impaired dri  ...[more]

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