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CRISPR/Cas9 基因组编辑技术在抗击人类致癌病毒中的意义。

The implication of CRISPR/Cas9 genome editing technology in combating human oncoviruses.

机构信息

School of Biological Sciences, University of the Punjab, Lahore, Pakistan.

Department of Zoology, University of the Punjab, Lahore, Pakistan.

出版信息

J Med Virol. 2019 Jan;91(1):1-13. doi: 10.1002/jmv.25292. Epub 2018 Sep 24.

Abstract

It is evidenced that 20% of all tumors in humans are caused by oncoviruses, including human papilloma viruses, Epstein-Barr virus, Kaposi sarcoma virus, human polyomaviruses, human T-lymphotrophic virus-1, and hepatitis B and C viruses. Human immunodeficiency virus is also involved in carcinogenesis, although not directly, but by facilitating the infection of many oncoviruses through compromising the immune system. Being intracellular parasites with the property of establishing latency and integrating into the host genome, these viruses are a therapeutic challenge for biomedical researchers. Therefore, strategies able to target nucleotide sequences within episomal or integrated viral genomes are of prime importance in antiviral or anticancerous armamentarium. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a powerful genome editing tool. Standing out as a precise and efficient oncoviruses method, it has been extensively applied in recent experimental ventures in the field of molecular medicine, particularly in combating infections including tumor inducing viruses. This review is aimed at collating the experimental and clinical advances in CRISPR/Cas9 technology in terms of its applications against oncoviruses. Primarily, it will focus on the application of CRISPR/Cas9 in combating tumor viruses, types of mechanisms targeted, and the significant outcomes till date. The technical pitfalls of the CRISPR/Cas9 and the comparative approaches in evaluating this technique with respect to other available alternatives are also described briefly. Furthermore, the review also discussed the clinical aspects and the ethical, legal, and social issues associated with the use of CRISPR/Cas9.

摘要

有证据表明,人类 20%的肿瘤是由致癌病毒引起的,包括人乳头瘤病毒、EB 病毒、卡波西肉瘤病毒、人类多瘤病毒、人类 T 淋巴细胞病毒-1 以及乙型和丙型肝炎病毒。人类免疫缺陷病毒也参与致癌作用,尽管不是直接的,但通过削弱免疫系统,促进许多致癌病毒的感染。这些病毒作为具有潜伏和整合到宿主基因组能力的细胞内寄生虫,是生物医学研究人员面临的治疗挑战。因此,能够针对附加体或整合病毒基因组内的核苷酸序列的策略在抗病毒或抗癌武器库中至关重要。最近,成簇规律间隔短回文重复(CRISPR)/CRISPR 相关蛋白 9(Cas9)已成为一种强大的基因组编辑工具。CRISPR/Cas9 作为一种精确而高效的致癌病毒方法,已在分子医学领域的最近实验性冒险中得到广泛应用,特别是在对抗包括肿瘤诱导病毒在内的感染方面。本综述旨在整理 CRISPR/Cas9 技术在抗癌病毒方面的实验和临床进展。它将主要侧重于 CRISPR/Cas9 在对抗肿瘤病毒、靶向的机制类型以及迄今为止的重要结果方面的应用。还简要描述了 CRISPR/Cas9 的技术缺陷以及相对于其他可用替代方案评估该技术的比较方法。此外,还讨论了 CRISPR/Cas9 的临床方面以及与使用相关的伦理、法律和社会问题。

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