A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae.
A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae.
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DOI：
10.1038/nbt.3439
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发表时间：
2016-01
影响因子：
46.9
通讯作者：
Nolan T
中科院分区：
文献类型：
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作者：
Hammond A;Galizi R;Kyrou K;Simoni A;Siniscalchi C;Katsanos D;Gribble M;Baker D;Marois E;Russell S;Burt A;Windbichler N;Crisanti A;Nolan T
基因驱动系统能够实现转基因的超级孟德尔遗传，有可能在几年内改变昆虫种群[AU请提供一个真实的估计，这似乎很模糊]。我们描述了在冈比亚按蚊（疟疾的主要载体）中起基因驱动系统作用的CRISPR-Cas9内切酶构建体[AU:OK?]我们确定了三个基因（AGAP005958， AGAP011377和AGAP007280），它们在破坏后会导致隐性女性不育表型，并在每个位点插入CRISPR-Cas9基因驱动构建，旨在靶向和编辑每个基因[AU:OK?]。对于每个目标位点，我们在分子水平上观察到强烈的基因驱动，遗传率为91%至99.6%。种群模型和笼子实验表明，靶向其中一个基因座AGAP007280的CRISPR-Cas9构建物满足了在昆虫种群中靶向雌性生殖的基因驱动的最低要求。这些发现可能会加速基因驱动的发展，从而将蚊子的数量控制在不支持疟疾传播的水平。
Gene-drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years [AU please provide a real estimate, this seems vague]. We describe CRISPR-Cas9 endonuclease constructs that function as gene-drive systems in Anopheles gambiae, the main vector for malaria [AU:OK?]. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene-drive constructs designed to target and edit each gene [AU:OK?]. For each locus targeted we observed strong gene drive at the molecular level, with transmission rates to progeny of 91 to 99.6%. Population modelling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to control suppress mosquito populations to levels that do not support malaria transmission.