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基于CRISPR-Cas的基因组编辑方法在抗人巨细胞病毒感染中的应用。

Applications of CRISPR-Cas-Based Genome Editing Approaches Against Human Cytomegalovirus Infection.

作者信息

Zhang Andra, Zhang Isadora, Liu Fenyong

机构信息

School of Public Health, University of California, Berkeley, CA 94720, USA.

Department of Molecular Cell Biology, University of California, Berkeley, CA 94720, USA.

出版信息

Biomedicines. 2025 Jun 30;13(7):1590. doi: 10.3390/biomedicines13071590.

Abstract

Human cytomegalovirus (HCMV), a globally ubiquitous herpesvirus with the ability to carry out both lytic productive and lifelong latent infections, is a major cause of congenital infections, often leading to intellectual disabilities and neurological disorders. Moreover, HCMV is an opportunistic pathogen commonly found in immunocompromised individuals such as organ transplant recipients, HIV-positive individuals, and cancer patients, causing severe and life-threatening complications. While effective in inhibiting viral lytic infection, current FDA-approved compounds cannot eliminate the latent viral genome and have little effect on viral latent infection. Developing novel antiviral therapeutic approaches to eliminate HCMV lytic and latent infections is a major public health priority for controlling HCMV infection and preventing viral-associated diseases. The genome-editing technology based on the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) RNA-guided nuclease system represents a novel and promising antiviral approach through modifying or destroying the genetic material of human viruses. This review summarizes the recently published progress in using the CRISPR-Cas approach to study and inhibit HCMV infections and discusses prospects for developing the CRISPR-based genome-editing technology for therapeutic applications against HCMV infection and associated diseases.

摘要

人巨细胞病毒(HCMV)是一种在全球广泛存在的疱疹病毒,能够进行裂解性增殖感染和终身潜伏感染,是先天性感染的主要原因,常导致智力残疾和神经紊乱。此外,HCMV是一种机会性病原体,常见于免疫功能低下的个体,如器官移植受者、HIV阳性个体和癌症患者,可引起严重的危及生命的并发症。虽然目前美国食品药品监督管理局(FDA)批准的化合物能有效抑制病毒的裂解性感染,但无法消除潜伏的病毒基因组,对病毒潜伏感染几乎没有作用。开发新的抗病毒治疗方法以消除HCMV的裂解性和潜伏性感染,是控制HCMV感染和预防病毒相关疾病的一项重大公共卫生优先事项。基于成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白(Cas)的RNA引导核酸酶系统的基因组编辑技术,代表了一种通过修饰或破坏人类病毒遗传物质的新型且有前景的抗病毒方法。本综述总结了最近发表的利用CRISPR-Cas方法研究和抑制HCMV感染的进展,并讨论了开发基于CRISPR的基因组编辑技术用于治疗HCMV感染及相关疾病的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d0d/12292117/abf48ea650ef/biomedicines-13-01590-g001.jpg

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