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

Rebeca Carballar-Lejarazú, Christian Ogaugwu, Taylor Tushar, Adam Kelsey, Thai Binh Pham, Jazmin Murphy, Hanno Schmidt, Yoosook Lee, Gregory C. Lanzaro, Anthony A. James

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)22805-22814
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number37
DOIs
StatePublished - Sep 15 2020

ASJC Scopus subject areas

  • General

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