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CRISPR 技术与 3D 基因组学的进展

The advances in CRISPR technology and 3D genome.

机构信息

Department of Pulmonary and Critical Care Medicine, The Second Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.

Zhongshan Hospital Institute of Clinical Science, Fudan University Medical School, Shanghai Institute of Clinical Bioinformatics Shanghai, China.

出版信息

Semin Cell Dev Biol. 2019 Jun;90:54-61. doi: 10.1016/j.semcdb.2018.07.009. Epub 2018 Aug 25.

Abstract

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system is a prokaryotic immune system that used to resist foreign genetic factors. It rapidly becomes the hot technology in life sciences and is applies for genome editing to solve the problem of genome-derived diseases. Using CRISPR/Cas technique, the biological DNA sequence can be repaired, cut, replaced, or added. It can effectively change the human stem cells and is expected to achieve results in the treatment. Compared with ZFN and TALEN genome editing techniques, CRISPR is more effective, accurate, and convenient. The application of CRISPR technique in three dimensional (3D) genome structure makes us understand the relationship between linear DNA sequence and 3D chromatin structure. Utilizing CRISPR/Cas9 genome editing to reverse or delete CTCF binding sites, to recognize changes of topological isomerism of the genome and interactions between chromatin loops. The purpose of this review is to introduce the characteristics and classification of the current CRISPR/Cas system, multiple functions, and potential therapeutic uses, as well as to outline the effect of the technique on chromatin loops by changing CTCF sites in 3D genomes. We will also briefly describe the importance of ethical dilemmas to be faced in CRISPR applications and provide a perspective for potential CRISPR considerations.

摘要

簇状规律间隔短回文重复序列(CRISPR)/CRISPR 相关蛋白(Cas)系统是一种原核免疫系统,用于抵抗外来遗传因素。它迅速成为生命科学领域的热门技术,并应用于基因组编辑以解决源于基因组的疾病问题。使用 CRISPR/Cas 技术,可以修复、切割、替换或添加生物 DNA 序列。它可以有效地改变人类干细胞,并有望在治疗中取得成果。与 ZFN 和 TALEN 基因组编辑技术相比,CRISPR 更加有效、准确和方便。CRISPR 技术在三维(3D)基因组结构中的应用使我们能够理解线性 DNA 序列与 3D 染色质结构之间的关系。利用 CRISPR/Cas9 基因组编辑来逆转或删除 CTCF 结合位点,以识别基因组拓扑异构变化和染色质环之间的相互作用。本综述旨在介绍当前 CRISPR/Cas 系统的特征和分类、多种功能和潜在的治疗用途,并概述通过改变 3D 基因组中的 CTCF 位点对染色质环的影响。我们还将简要描述在 CRISPR 应用中面临的伦理困境的重要性,并为潜在的 CRISPR 考虑提供一个视角。

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