工程抗病毒传感器锁定受感染的蚊子

IF 3.7 4区 生物学 Q2 GENETICS & HEREDITY
Elena Dalla Benetta, Adam J López-Denman, Hsing-Han Li, Reem A Masri, Daniel J Brogan, Michelle Bui, Ting Yang, Ming Li, Michael Dunn, Melissa J Klein, Sarah Jackson, Kyle Catalan, Kim R Blasdell, Priscilla Tng, Igor Antoshechkin, Luke S Alphey, Prasad N Paradkar, Omar S Akbari
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引用次数: 0

摘要

病媒疾病负担的不断增加对全球健康构成了重大风险,因此针对蚊子的创新工具至关重要。CRISPR-Cas 技术在开发用于操纵各种真核生物基因组的强大工具方面发挥了至关重要的作用。虽然大量工作集中在利用第二类第二型 CRISPR-Cas9 系统进行 DNA 靶向,但这些模式无法靶向 RNA 分子,限制了它们在对付 RNA 病毒方面的作用。最近,Cas13 家族作为一种有效的 RNA 靶向工具出现了;然而,这种技术在蚊子(尤其是埃及伊蚊)中的应用尚未完全实现。在这项研究中,我们设计了一种名为 REAPER(vRNA 表达激活有毒效应核糖核酸酶)的抗病毒策略,它利用了 CRISPR-Cas13 的可编程 RNA 靶向能力及其强大的附带活性。REAPER 隐藏在蚊子体内,直到吸食了有传染性的血食。一旦感染目标病毒 RNA,REAPER 就会激活,触发对目标虫媒病毒(如基孔肯雅病毒)的程序性破坏。因此,Cas13 介导的 RNA 靶向能显著减少病毒复制和病毒感染流行,其杂乱的附带活性甚至能在几天内杀死受感染的蚊子。这项创新的 REAPER 技术为抗击蚊虫病毒传播的有效分子遗传工具库增添了新的成员。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Engineered Antiviral Sensor Targets Infected Mosquitoes.

Escalating vector disease burdens pose significant global health risks, as such innovative tools for targeting mosquitoes are critical. CRISPR-Cas technologies have played a crucial role in developing powerful tools for genome manipulation in various eukaryotic organisms. Although considerable efforts have focused on utilizing class II type II CRISPR-Cas9 systems for DNA targeting, these modalities are unable to target RNA molecules, limiting their utility against RNA viruses. Recently, the Cas13 family has emerged as an efficient tool for RNA targeting; however, the application of this technique in mosquitoes, particularly Aedes aegypti, has yet to be fully realized. In this study, we engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR-Cas13 and its potent collateral activity. REAPER remains concealed within the mosquito until an infectious blood meal is uptaken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13-mediated RNA targeting significantly reduces viral replication and viral prevalence of infection, and its promiscuous collateral activity can even kill infected mosquitoes within a few days. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.

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来源期刊
CRISPR Journal
CRISPR Journal Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
6.30
自引率
2.70%
发文量
76
期刊介绍: In recognition of this extraordinary scientific and technological era, Mary Ann Liebert, Inc., publishers recently announced the creation of The CRISPR Journal -- an international, multidisciplinary peer-reviewed journal publishing outstanding research on the myriad applications and underlying technology of CRISPR. Debuting in 2018, The CRISPR Journal will be published online and in print with flexible open access options, providing a high-profile venue for groundbreaking research, as well as lively and provocative commentary, analysis, and debate. The CRISPR Journal adds an exciting and dynamic component to the Mary Ann Liebert, Inc. portfolio, which includes GEN (Genetic Engineering & Biotechnology News) and more than 80 leading peer-reviewed journals.
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