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基因组编辑方法与应用:关于CRISPR技术及其在癌症中作用的简要综述

Genome-editing approaches and applications: a brief review on CRISPR technology and its role in cancer.

作者信息

Siva Narmadhaa, Gupta Sonal, Gupta Ayam, Shukla Jayendra Nath, Malik Babita, Shukla Nidhi

机构信息

Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Statue Circle, Jaipur, India.

Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindari, Ajmer, India.

出版信息

3 Biotech. 2021 Mar;11(3):146. doi: 10.1007/s13205-021-02680-4. Epub 2021 Feb 26.

Abstract

The development of genome-editing technologies in 1970s has discerned a new beginning in the field of science. Out of different genome-editing approaches such as Zing-finger nucleases, TALENs, and meganucleases, clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR/Cas9) is a recent and versatile technology that has the ability of making changes to the genome of different organisms with high specificity. Cancer is a complex process that is characterized by multiple genetic and epigenetic changes resulting in abnormal cell growth and proliferation. As cancer is one of the leading causes of deaths worldwide, a large number of studies are done to understand the molecular mechanisms underlying the development of cancer. Because of its high efficiency and specificity, CRISPR/Cas9 has emerged as a novel and powerful tool in the field of cancer research. CRISPR/Cas9 has the potential to accelerate cancer research by dissecting tumorigenesis process, generating animal and cellular models, and identify drug targets for chemotherapeutic approaches. However, despite having tremendous potential, there are certain challenges associated with CRISPR/Cas9 such as safe delivery to the target, potential off-target effects and its efficacy which needs to be addressed prior to its clinical application. In this review, we give a gist of different genome-editing technologies with a special focus on CRISPR/Cas9 development, its mechanism of action and its applications, especially in different type of cancers. We also highlight the importance of CRISPR/Cas9 in generating animal models of different cancers. Finally, we present an overview of the clinical trials and discuss the challenges associated with translating CRISPR/Cas9 in clinical use.

摘要

20世纪70年代基因组编辑技术的发展开启了科学领域的新篇章。在锌指核酸酶、转录激活因子样效应物核酸酶和巨核酸酶等不同的基因组编辑方法中,成簇规律间隔短回文重复序列-CRISPR相关蛋白9(CRISPR/Cas9)是一项最新且通用的技术,它能够以高特异性对不同生物体的基因组进行改造。癌症是一个复杂的过程,其特征是多种基因和表观遗传变化导致细胞异常生长和增殖。由于癌症是全球主要死因之一,因此开展了大量研究以了解癌症发生发展的分子机制。由于其高效性和特异性,CRISPR/Cas9已成为癌症研究领域一种新型且强大的工具。CRISPR/Cas9有潜力通过剖析肿瘤发生过程、建立动物和细胞模型以及识别化疗方法的药物靶点来加速癌症研究。然而,尽管CRISPR/Cas9具有巨大潜力,但它也存在一些挑战,如安全递送至靶点、潜在的脱靶效应及其疗效,在临床应用之前需要解决这些问题。在这篇综述中,我们简要介绍了不同的基因组编辑技术,特别关注CRISPR/Cas9的发展、其作用机制及其应用,尤其是在不同类型癌症中的应用。我们还强调了CRISPR/Cas9在建立不同癌症动物模型中的重要性。最后,我们概述了临床试验,并讨论了将CRISPR/Cas9转化为临床应用所面临的挑战。

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