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A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes.

Abstract：

:In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all Anopheles mosquitoes so far analyzed. We found that CRISPR-Cas9-targeted disruption of the intron 4-exon 5 boundary aimed at blocking the formation of functional AgdsxF did not affect male development or fertility, whereas females homozygous for the disrupted allele showed an intersex phenotype and complete sterility. A CRISPR-Cas9 gene drive construct targeting this same sequence spread rapidly in caged mosquitoes, reaching 100% prevalence within 7-11 generations while progressively reducing egg production to the point of total population collapse. Owing to functional constraint of the target sequence, no selection of alleles resistant to the gene drive occurred in these laboratory experiments. Cas9-resistant variants arose in each generation at the target site but did not block the spread of the drive.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Kyrou K,Hammond AM,Galizi R,Kranjc N,Burt A,Beaghton AK,Nolan T,Crisanti A

doi

10.1038/nbt.4245

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1062-1066

issue

11

eissn

1087-0156

issn

1546-1696

pii

nbt.4245

journal_volume

36

pub_type

杂志文章

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