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使基因驱动可生物降解。

Making gene drive biodegradable.

机构信息

Department of Industrial and Systems Engineering, Texas A&M University, College Station, TX 77843, USA.

Department of Entomology and Agrilife Research, Texas A&M University, College Station, TX 77843, USA.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2021 Feb 15;376(1818):20190804. doi: 10.1098/rstb.2019.0804. Epub 2020 Dec 28.

Abstract

Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.

摘要

基因驱动系统长期以来一直被用于改变蚊子种群,从而防治疟疾和登革热。在实验室实验中已经开发出了强大的基因驱动系统,但除非能够通过严格的基于现场的测试证明其可以被接受,否则可能永远不会在实践中使用。这种测试很复杂,因为预计从自然界中去除基因驱动转基因会很困难。在这里,我们考虑将自我消除机制纳入基于同源的基因驱动转基因的设计中。这种方法不仅导致了基因驱动转基因的切除,而且还产生了一个对基因驱动进一步作用具有抗性的转基因免费等位基因。引人注目的是,我们的模型表明,这种机制以适度的速率(10%)作为单一组件系统的一部分,足以导致即使是最强大的基于同源的基因驱动转基因的快速逆转,而无需进一步的补救措施。建模还表明,与基因驱动转基因本身不同,自我消除的转基因方法预计能够容忍相当高的失败率。因此,自我消除技术可以通过在自然界中对基因驱动转基因的存在设定严格的时间限制来允许对基因驱动进行严格的基于现场的测试,从而使它们基本上可生物降解。本文是主题为“蚊媒疾病的新型控制策略”的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de26/7776940/784ea517041a/rstb20190804-g1.jpg

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