Chemical Controllable Gene Drive in Drosophila

Chemical Controllable Gene Drive in Drosophila
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DOI:
10.1021/acssynbio.0c00117
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发表时间:
2020-09-18
影响因子:
4.7
通讯作者:
Kim, Hyongbum H.
Kim, Hyongbum H.
中科院分区:
生物学2区
文献类型:
--
作者:
Chae, Dongwoo;Lee, Junwon;Kim, Hyongbum H.

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通过超孟德尔遗传传播转基因的基因驱动系统有可能控制虫媒疾病和农业害虫。然而,人们对不可预见的生态后果提出了担忧,并提出了防止不良基因驱动效应的方法。在这里,我们报告了化学诱导的基因驱动控制。我们制备了一种基于 CRISPR 的基因驱动系统,可以通过位点特异性重组酶 Rippase 去除,Rippase 的表达是由果蝇中的化学物质 RU486 诱导的。将果蝇暴露于 RU486 会导致每一代基因驱动元件去除 7-12%,导致基因驱动蝇繁殖显着减少。数学建模和模拟表明,我们的系统比之前报道的基因驱动控制系统具有多种优势。我们的化学控制系统可以根据生态状况和人类需求,为基因驱动效应的可逆控制提供原理验证。
Gene drive systems that propagate transgenes via super-Mendelian inheritance can potentially control insect-borne diseases and agricultural pests. However, concerns have been raised regarding unforeseen ecological consequences, and methods that prevent undesirable gene drive effects have been proposed. Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted in 7-12% removal of gene drive elements at each generation, leading to a significant reduction in gene drive-fly propagation. Mathematical modeling and simulation suggest that our system offers several advantages over a previously reported gene drive control system. Our chemical control system can provide a proof-of-principle for the reversible control of gene drive effects depending on ecological status and human needs.