Development of a confinable gene drive system in the human disease vector Aedes aegypti
Development of a confinable gene drive system in the human disease vector Aedes aegypti
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人类疾病媒介埃及伊蚊的受限基因驱动系统的开发
作者：
Ming Li;Ting Yang;Nikolay P. Kandul;Michelle Bui;Stephanie Gamez;Robyn R. Raban;Jared B. Bennett;H. Sánchez C.;G. Lanzaro;H. Schmidt;Yoosook Lee;John M. Marshall;O. Akbari
埃及伊蚊是导致黄热病、登革热、寨卡和基孔肯雅病的许多虫媒病毒的主要蚊子媒介，每年感染数百万人的人数越来越多。随着感染负担的不断增加和传统控制方法的相对失败，制定创新的控制措施变得至关重要。基因驱动的使用最近引发了对蚊子种群遗传控制的极大热情，然而在Ae中还没有开发出这样的系统。埃及人。为了填补这一空白并证明在Ae中的疗效。埃及，在这里，我们开发了几种基于CRISPR的分裂基因驱动器用于该载体。由于切割率高达100%，传播率高达94%，数学模型预测这些系统可以将抗病原体效应基因传播到野生Ae中。以安全、可控制和可逆的方式向埃及人群体提供适合于实地试验并有效控制疾病的药物。这些发现可以加速与效应子相关的基因驱动的发展，从而可以安全地控制野生的Ae种群。埃及政府将采取措施防止病原体在当地传播。重要性声明Ae.埃及伊蚊是一种全球分布的虫媒病毒，每年向数百万人传播致命病原体。目前的控制方法是不够的，因此需要创新和实施新技术。为了提供控制这种害虫的新工具，我们在这个物种中设计和测试了几种分裂基因驱动器。这些驱动器以非常高的效率运作，并可能提供一种工具来填补控制这一矢量的空白。总之，我们的研究结果为未来效应器连接的分离驱动技术的可行性提供了令人信服的前进道路，这些技术可以有助于安全，持续的控制和潜在的消除该物种传播的病原体。
Aedes aegypti, the principal mosquito vector for many arboviruses that causes yellow fever, dengue, Zika, and chikungunya, increasingly infects millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has recently sparked significant enthusiasm for the genetic control of mosquito populations, however no such system has been developed in Ae. aegypti. To fill this void and demonstrate efficacy in Ae. aegypti, here we develop several CRISPR-based split-gene drives for use in this vector. With cleavage rates up to 100% and transmission rates as high as 94%, mathematical models predict that these systems could spread anti-pathogen effector genes into wild Ae. aegypti populations in a safe, confinable and reversible manner appropriate for field trials and effective for controlling disease. These findings could expedite the development of effector-linked gene drives that could safely control wild populations of Ae. aegypti to combat local pathogen transmission. Significance Statement Ae. aegypti is a globally distributed arbovirus vector spreading deadly pathogens to millions of people annually. Current control methods are inadequate and therefore new technologies need to be innovated and implemented. With the aim of providing new tools for controlling this pest, here we engineered and tested several split gene drives in this species. These drives functioned at very high efficiency and may provide a tool to fill the void in controlling this vector. Taken together, our results provide compelling path forward for the feasibility of future effector-linked split-drive technologies that can contribute to the safe, sustained control and potentially the elimination of pathogens transmitted by this species.
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DOI：
10.1073/pnas.0600479103
发表时间：
2006-03-14
影响因子：
11.1
作者：
Franz, AWE;Sanchez-Vargas, I;Olson, KE
通讯作者：
Olson, KE
小鼠zygotes中CRISPR/Cas9 RNA引起的体细胞镶嵌和等位基因复杂性。
影响因子：
2.7
作者：
Yen, Shuo-Ting;Zhang, Min;Deng, Jian Min;Usman, Shireen J.;Smith, Chad N.;Parker-Thornburg, Jan;Swinton, Paul G.;Martin, James F.;Behringer, Richard R.
通讯作者：
Behringer, Richard R.
DOI：
10.1073/pnas.1805278115
发表时间：
2018-10-02
影响因子：
11.1
作者：
Oberhofer G;Ivy T;Hay BA
通讯作者：
Hay BA
蚊子埃及埃及的基因组工程与CRISPR-Cas9。
影响因子：
8.8
作者：
Kistler KE;Vosshall LB;Matthews BJ
通讯作者：
Matthews BJ
影响因子：
3.5
作者：
STEINHAUER, DA;DOMINGO, E;HOLLAND, JJ
通讯作者：
HOLLAND, JJ