Evaluating strategies for reversing CRISPR-Cas9 gene drives.
Evaluating strategies for reversing CRISPR-Cas9 gene drives.
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DOI：
10.1038/s41598-017-10633-2
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发表时间：
2017-09-08
影响因子：
4.6
通讯作者：
Gould F
中科院分区：
文献类型：
--
作者：
Vella MR;Gunning CE;Lloyd AL;Gould F
基因驱动偏向于基因的遗传，因此即使基因没有赋予适应性益处，它也会在种群中增加频率。由于最近使用CRISPR-Cas9系统作为驱动机制的原理实验的证明，对工程基因驱动的环境释放重新产生了兴趣。然而，释放改性生物是有争议的，特别是当驱动机制理论上可以改变一个物种的所有个体时。因此，如果出现问题，则期望具有反转驱动的对策。已经提出和/或开发了几种用于限制或消除基因驱动的遗传机制，包括合成抗性、逆转驱动和免疫逆转驱动。虽然对这些机制功效的预测一直很乐观，但我们缺乏对其预期动态的详细分析。建立了驱力群体遗传学的离散时间模型，并提出了相应的遗传对策。驱动器反转的功效因对策而异。对于某些参数值，该模型预测意想不到的行为，包括多态平衡和振荡动力学。释放含有遗传对策的个体的时间和数量可以极大地影响结果。研究人员和管理人员对对策的选择将取决于目标人群的具体目标和人群参数。
A gene drive biases inheritance of a gene so that it increases in frequency within a population even when the gene confers no fitness benefit. There has been renewed interest in environmental releases of engineered gene drives due to recent proof of principle experiments with the CRISPR-Cas9 system as a drive mechanism. Release of modified organisms, however, is controversial, especially when the drive mechanism could theoretically alter all individuals of a species. Thus, it is desirable to have countermeasures to reverse a drive if a problem arises. Several genetic mechanisms for limiting or eliminating gene drives have been proposed and/or developed, including synthetic resistance, reversal drives, and immunizing reversal drives. While predictions about efficacy of these mechanisms have been optimistic, we lack detailed analyses of their expected dynamics. We develop a discrete time model for population genetics of a drive and proposed genetic countermeasures. Efficacy of drive reversal varies between countermeasures. For some parameter values, the model predicts unexpected behavior including polymorphic equilibria and oscillatory dynamics. The timing and number of released individuals containing a genetic countermeasure can substantially impact outcomes. The choice among countermeasures by researchers and regulators will depend on specific goals and population parameters of target populations.
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DOI：
10.1126/science.aaa5945
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gantz VM;Bier E
通讯作者：
Bier E
影响因子：
64.5
作者：
Zetsche B;Gootenberg JS;Abudayyeh OO;Slaymaker IM;Makarova KS;Essletzbichler P;Volz SE;Joung J;van der Oost J;Regev A;Koonin EV;Zhang F
通讯作者：
Zhang F
影响因子：
64.5
作者：
Hsu PD;Lander ES;Zhang F
通讯作者：
Zhang F
DOI：
10.1002/bies.201500102
发表时间：
2016-01
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology
影响因子：
--
作者：
Gantz VM;Bier E
通讯作者：
Bier E
影响因子：
2
作者：
Durrett, R;Levin, S
通讯作者：
Levin, S