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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 publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





22805 - 22814


cage trials, guide RNA polymorphisms, load, nontarget, off-target, Alleles, Animals, Animals, Genetically Modified, Anopheles, CRISPR-Cas Systems, Gene Drive Technology, Genetics, Population, High-Throughput Nucleotide Sequencing, Malaria, Mosquito Control, Mosquito Vectors, Phenotype, Transgenes