调控CRISPR-Cas9系统用于基因编辑的研究进展

doi:10.6023/A20040131

化学学报 ›› 2020, Vol. 78 ›› Issue (7): 634-641.DOI: 10.6023/A20040131 上一篇下一篇

综述

调控CRISPR-Cas9系统用于基因编辑的研究进展

公少华, 李娜, 唐波

山东师范大学化学化工与材料科学学院分子与纳米探针教育部重点实验室化学成像功能探针山东省高等学校协同创新中心山东师范大学分子与纳米科学研究院济南 250014

投稿日期:2020-04-29 发布日期:2020-06-11
通讯作者: 李娜 E-mail:lina@sdnu.edu.cn
作者简介:公少华,山东师范大学化学化工与材料科学学院在读博士研究生,主要从事功能纳米探针的构建及生物应用研究工作.
李娜,2009年于山东大学毕业获得理学博士学位,山东师范大学化学化工与材料科学学院教授、博士生导师,国家自然科学基金优秀青年基金获得者,教育部"长江学者奖励计划"青年学者,山东省自然科学基金杰出青年基金获得者,泰山学者青年专家.主要从事新型功能纳米荧光探针的设计合成及其用于活细胞、活体内活性物种的检测、成像及可控药物输送的研究.2018年获得国家自然科学二等奖(第五位),2016年获山东省自然科学一等奖(第三位)和山东省高等学校优秀科研成果自然科学一等奖(第一位).
唐波,1994年毕业于南开大学化学系,获理学博士,山东师范大学化学化工与材料科学学院教授、博士生导师,首届十佳全国优秀科技工作者提名奖获得者,973计划首席科学家,国家杰出青年科学基金获得者,"新世纪百千万人才工程"国家级人选.现主要从事分子及纳米荧光探针的合成及其在生物成像中的应用、绿色化工、荧光材料合成及太阳能化学转化与储存等方面研究工作.荣获国家自然科学二等奖1项,国家科技进步奖二等奖2项,山东省自然科学奖一等奖1项,山东省科技进步奖一等奖2项.
基金资助:
项目受国家重点研发计划（No.2019YFA0210100）、国家自然科学基金（Nos.21535004，91753111，21927881，21874086，21775094）、山东省重点研发计划（No.2018YFJH0502）和山东省高等学校青年创新科技项目（No.2019KJC022）资助.

Recent Progress in Regulating CRISPR-Cas9 System for Gene Editing

Gong Shaohua, Li Na, Tang Bo

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China

Received:2020-04-29 Published:2020-06-11
Supported by:
Project supported by the National Key R&D Program of China (No. 2019YFA0210100), the National Natural Science Foundation of China (Nos. 21535004, 91753111, 21927881, 21874086, 21775094), the Key Research and Development Program of Shandong Province (No. 2018YFJH0502), and the Youth Innovation Science and Technology Program of Higher Education Institution of Shandong Province (No. 2019KJC022).

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摘要/Abstract

基于操作简便、成本低、快捷高效的优势，规律间隔成簇短回文重复序列及其相关核酸酶（CRISPR-Cas9）系统在基因编辑的基础研究和临床医学方面起到了极为重要的推动作用.在时空维度上调控CRISPR-Cas9发挥功能，对于减少CRISPR-Cas9系统的脱靶效应，提高基因编辑的特异性具有重要意义.本综述介绍了近年来利用化学分子以及光调控CRISPR-Cas9系统发挥功能，进而调控基因编辑的研究进展，并探讨了CRISPR-Cas9调控的前景和面临的挑战.

关键词: CRISPR-Cas9, 基因编辑, 特异性, 脱靶效应, 调控

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system is an adaptive immune system used by many bacteria and archaea to defend the invasion of exogenous nucleic acids. CRISPR-Cas system in different species of archaea and bacteria has different components and working mechanisms. Depending on the numbers of effector proteins, CRISPR-Cas systems can be classified into two major types. CRISPR-Cas9, which is composed of Cas9 nuclease and sgRNA, belongs to class Ⅱ CRISPR-Cas system and can be used as a powerful genome editing tool. It can target and cleave the DNA sequence which contains protospacer adjacent motif (PAM, 5'-NGG-3') sequence. The DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or nonhomologous end joining (NHEJ) mechanism. Insertions or deletions (indels) can be introduced at targeted loci in the DSBs repair process. Due to its convenience, low cost and high efficiency, CRISPR-Cas9 has played an important role in promoting the development of gene editing in basic research and clinical medicine. However, off-target effect of CRISPR-Cas9 should not be neglected. The CRISPR-Cas9 is able to cleave the target DNA even when the sgRNA imperfectly matches with the target DNA, leading to the unwanted indels at nontargeted DNA loci, which limits the further application of genome editing, especially for the treatment of genetic diseases. Therefore, it is significant to reduce the off-target cleavage effect of CRISPR-Cas9. Many efforts have been devoted to realize the reduced off-target effect of CRISPR-Cas9. Among these methods, regulating the function of CRISPR-Cas9 at spatiotemporal dimension is a potential strategy to reduce the off-target effect of CRISPR-Cas9 system and improve the specificity of gene editing. In this review, we summarized the research advances in regulating the function of CRISPR-Cas9 and discussed the prospects and challenges of CRISPR-Cas9 regulation.

Key words: CRISPR-Cas9, gene editing, specificity, off-target effect, regulation

引用此文

公少华, 李娜, 唐波. 调控CRISPR-Cas9系统用于基因编辑的研究进展[J]. 化学学报, 2020, 78(7): 634-641.

Gong Shaohua, Li Na, Tang Bo. Recent Progress in Regulating CRISPR-Cas9 System for Gene Editing[J]. Acta Chimica Sinica, 2020, 78(7): 634-641.

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调控CRISPR-Cas9系统用于基因编辑的研究进展

Recent Progress in Regulating CRISPR-Cas9 System for Gene Editing

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