CRISPR基因组编辑技术在传染病致病机理研究和防诊治中的应用

doi:10.16288/j.yczz.23-206

遗传 ›› 2023, Vol. 45 ›› Issue (11): 950-962.doi: 10.16288/j.yczz.23-206

CRISPR基因组编辑技术在传染病致病机理研究和防诊治中的应用

杨臻嵘^1,²(), 周钢桥^1,²()

1.中国科学技术大学生命科学学院，生命科学与医学部，合肥 230022
2.军事科学院军事医学研究院辐射医学研究所，医学蛋白质组全国重点实验室，国家蛋白质科学中心，北京 100850

收稿日期:2023-07-31 修回日期:2023-10-06 出版日期:2023-11-20 发布日期:2023-10-24
通讯作者: 周钢桥 E-mail:yangzr@mail.ustc.edu.cn;zhougq114@126.com
作者简介:杨臻嵘，博士研究生，专业方向：细胞生物学。E-mail: yangzr@mail.ustc.edu.cn。
基金资助:
广州实验室应急攻关项目(EKPG21-19);Supported by the Emergency Key Program of Guangzhou Laboratory No(EKPG21-19)

The application of CRISPR genome editing technologies in the pathogenesis studies, diagnosis, prevention and treatment of infectious diseases

Zhenrong Yang^1,²(), Gangqiao Zhou^1,²()

1. School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China
2. State Key Lab of Proteomics, National Center for Protein Sciences at Beijing, Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China

Received:2023-07-31 Revised:2023-10-06 Published:2023-11-20 Online:2023-10-24
Contact: Gangqiao Zhou E-mail:yangzr@mail.ustc.edu.cn;zhougq114@126.com

摘要/Abstract

摘要：

CRISPR基因组编辑技术在基因操作和传染病研究等方面展现出巨大的应用前景，对于有效控制和治愈传染病具有重要价值。通过其构建的细胞、类器官和动物疾病模型，为探索传染病相关分子机制提供了极大便利。CRISPR筛选技术使得高通量鉴定传染病相关风险因子成为可能。基于CRISPR的新型分子诊断工具为病原体的检测提供了更灵敏和快速的方法。利用CRISPR工具敲入抗性基因或破坏风险基因和病毒基因组，有望实现预防或治疗传染病。本综述讨论了CRISPR基因组编辑技术在疾病模型制备、传染病风险因子筛选、病原体诊断和传染病防治中的应用，以期为后续传染病的研究和防诊治提供参考。

关键词: 传染病, CRISPR, 致病机理, 诊断

Abstract:

The CRISPR genome editing technology shows great application prospects in gene manipulation and infectious disease research, and is of great value for effective control and cure of infectious diseases. It has been utilized to generate specific disease models in cells, organoids and animals, which provide great convenience for research into the molecular mechanisms associated with infectious diseases. CRISPR screening technology enables high-throughput identification of risk factors. New molecular diagnostic tools based on CRISPR offer a more sensitive and faster method for detecting pathogens. The use of CRISPR tools to introduce resistance genes or to specifically destroy risk genes and virus genomes is intended to help prevent or treat infectious diseases. This review discusses the application of CRISPR genome editing technologies in the construction of disease models, screening of risk factors, pathogen diagnosis, and prevention and treatment of infectious diseases, thereby providing a reference for follow-up research in pathogenesis, diagnosis, prevention and treatment of infectious diseases.

Key words: infectious diseases, CRISPR, pathogenesis, diagnosis

杨臻嵘, 周钢桥. CRISPR基因组编辑技术在传染病致病机理研究和防诊治中的应用[J]. 遗传, 2023, 45(11): 950-962.

Zhenrong Yang, Gangqiao Zhou. The application of CRISPR genome editing technologies in the pathogenesis studies, diagnosis, prevention and treatment of infectious diseases[J]. Hereditas(Beijing), 2023, 45(11): 950-962.

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	牛煦然, 尹树明, 陈曦, 邵婷婷, 李大力. 基因编辑技术及其在疾病治疗中的研究进展. 遗传, 2019, 41(7): 582-598.

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类别	HEs	ZFNs	TALENs	CRISPR/Cas
作用方式	蛋白质- DNA	蛋白质- DNA	蛋白质- DNA	RNA-DNA或RNA-RNA
操作难度	困难	困难	中等	简单
成本	高	中等	中等	低
多靶点编辑难度	困难	困难	困难	简单

应用类型	应用内容	实例	参考文献
诊断	检测病原体核酸分子	利用基于CRISPR/Cas13a或CRISPR/Cas12b的核酸检测系统SHERLOCK/SHERLOCKv2检测ZIKV、DENV、WNV、YFV、SARS-CoV-2、大肠杆菌、铜绿假单胞菌和肺炎克雷伯菌；	[51, 79, 80,81, 82]
诊断	检测病原体核酸分子	利用基于CRISPR/Cas12a的DNA分子检测系统DETECTR检测HPV。	[48]
预防	改造病原携带者基因组	利用CRISPR/Cas9工具将针对人类恶性疟原虫的单链抗体基因(m1C3，m2A10)敲入斯氏按蚊印度品系的胚胎中，获得携带有抗虫基因的后代；	[85]
预防	改造病原携带者基因组	利用CRISPR/Cas9工具靶向生育相关的基因(雌性冈比亚按蚊的dsxF基因，雄性埃及伊蚊的B2t基因)，使突变蚊子不能产生后代。	[86,87]
治疗	编辑细胞基因组/病毒基因组	利用CRISPR/Cas9工具编辑细胞的CCR5基因，或同时切除整合到细胞基因组上的HIV-1 DNA，以降低病毒载量；	[88,89]
		利用CRISPR/Cas9工具切割受HBV感染细胞中的cccDNA，以减少总病毒DNA和cccDNA；	[90~92]
		利用CRISPR/Cas9工具修饰受HSV-1感染细胞中的病毒基因组DNA，以减弱病毒毒力；	[93,94]
		利用基于CRISPR/Cas13a的集诊断与抗病毒治疗于一体的CARVER系统检测并切割受LCMV、IAV或VSV感染细胞中的病毒基因组，以降低病毒RNA水平。	[95]

CRISPR基因组编辑技术在传染病致病机理研究和防诊治中的应用

The application of CRISPR genome editing technologies in the pathogenesis studies, diagnosis, prevention and treatment of infectious diseases

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