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CRISPR/Cas9——对抗传染病的终极武器?

CRISPR/Cas9-The ultimate weapon to battle infectious diseases?

作者信息

Doerflinger M, Forsyth W, Ebert G, Pellegrini M, Herold M J

机构信息

Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.

出版信息

Cell Microbiol. 2017 Feb;19(2). doi: 10.1111/cmi.12693. Epub 2016 Dec 6.

DOI:10.1111/cmi.12693
PMID:27860197
Abstract

Infectious diseases are a leading cause of death worldwide. Novel therapeutics are urgently required to treat multidrug-resistant organisms such as Mycobacterium tuberculosis and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus-1 and hepatitis B virus. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, which has revolutionized biomedical research, holds great promise for the identification and validation of novel drug targets. Since its discovery as an adaptive immune system in prokaryotes, the CRISPR/Cas9 system has been developed into a multi-faceted genetic modification tool, which can now be used to induce gene deletions or specific gene insertions, such as conditional alleles or endogenous reporters in virtually any organism. The generation of CRISPR/Cas9 libraries that can be used to perform phenotypic whole genome screens provides an important new tool that will aid in the identification of critical host factors involved in the pathogenesis of infectious diseases. In this review, we will discuss the development and recent applications of the CRISPR/Cas9 system used to identify novel regulators, which might become important in the fight against infectious diseases.

摘要

传染病是全球主要死因之一。迫切需要新型疗法来治疗耐多药病原体,如结核分枝杆菌,并减轻由急性感染(如疟疾和登革热病毒)以及慢性感染(如人类免疫缺陷病毒1型和乙型肝炎病毒)所导致的发病率和死亡率。成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9)系统彻底改变了生物医学研究,在新型药物靶点的识别和验证方面具有巨大潜力。自从作为原核生物的适应性免疫系统被发现以来,CRISPR/Cas9系统已发展成为一种多方面的基因编辑工具,现在可用于在几乎任何生物体中诱导基因缺失或特定基因插入,如条件性等位基因或内源性报告基因。可用于进行表型全基因组筛选的CRISPR/Cas9文库的产生提供了一种重要的新工具,将有助于识别参与传染病发病机制的关键宿主因子。在本综述中,我们将讨论用于识别新型调节因子的CRISPR/Cas9系统的发展和近期应用,这些调节因子可能在抗击传染病中发挥重要作用。

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