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用于治疗新冠肺炎的先进小干扰RNA疗法的设计

Design of advanced siRNA therapeutics for the treatment of COVID-19.

作者信息

Niktab Iman, Haghparast Maryam, Beigi Mohammad-Hossein, Megraw Timothy L, Kiani Amirkianoosh, Ghaedi Kamran

机构信息

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science & Technology, University of Isfahan, Isfahan, Iran.

Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.

出版信息

Meta Gene. 2021 Sep;29:100910. doi: 10.1016/j.mgene.2021.100910. Epub 2021 May 8.

Abstract

COVID-19 is a newly emerged viral disease that is currently affecting the whole globe. A variety of therapeutic approaches are underway to block the SARS-CoV-2 virus. Among these methods, siRNAs could be a safe and specific option, as they have been tested against other viruses. siRNAs are a class of inhibitor RNAs that act promisingly as mRNA expression blockers and they can be designed to interfere with viral mRNA to block virus replication. In order to do this, we designed and evaluated the efficacy of six highly specific siRNAs, which target essential viral mRNAs with no predicted human genome off-targets. We observed a significant reduction in the copy number viral mRNAs after treatment with the siRNAs, and are expected to inhibit virus replication. We propose siRNAs as a potential co-therapy for acute SARS-CoV-2 infection.

摘要

新冠病毒病(COVID-19)是一种新出现的病毒性疾病,目前正在影响全球。正在采取多种治疗方法来阻断严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒。在这些方法中,小干扰RNA(siRNAs)可能是一种安全且特异的选择,因为它们已针对其他病毒进行过测试。小干扰RNA是一类抑制性RNA,有望作为信使核糖核酸(mRNA)表达阻断剂发挥作用,并且可以设计它们来干扰病毒信使核糖核酸以阻断病毒复制。为了实现这一点,我们设计并评估了六种高度特异的小干扰RNA的效果,这些小干扰RNA靶向基本的病毒信使核糖核酸,且无预测的人类基因组脱靶效应。在用小干扰RNA处理后,我们观察到病毒信使核糖核酸的拷贝数显著减少,预计可抑制病毒复制。我们提出将小干扰RNA作为急性SARS-CoV-2感染的一种潜在联合治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090d/8106235/ca87443f83f0/gr1_lrg.jpg

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