基因组编辑技术在精准医学中的应用

doi:10.16288/j.yczz.16-395

遗传 ›› 2017, Vol. 39 ›› Issue (3): 177-188.doi: 10.16288/j.yczz.16-395

基因组编辑技术在精准医学中的应用

李爽¹(),杨圆圆¹,邱艳¹,陈彦好¹,徐璐薇²,丁秋蓉¹

1. 中国科学院上海生命科学研究院营养科学研究所,上海 200031
2. 江苏省泰州市中医院,泰州 225300

收稿日期:2016-11-23 修回日期:2017-01-21 出版日期:2017-03-20 发布日期:2017-02-10
基金资助:
上海市浦江人才计划项目(15PJ1409200);中国科学院百人计划和国家青年千人计划项目资助

Applications of genome editing tools in precision medicine research

Shuang Li¹(),Yuanyuan Yang¹,Yan Qiu¹,Yanhao Chen¹,Luwei Xu²,Qiurong Ding¹

1. Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Shanghai 200031, China
2. Taizhou Hospital of Traditional Chinese Medicine, Taizhou 225300, China

Received:2016-11-23 Revised:2017-01-21 Online:2017-03-20 Published:2017-02-10
Supported by:
the Shanghai Pujiang Talent Program(15PJ1409200);CAS Hundred Talent Program and the National Young Scientist Thousand Talent Program

摘要/Abstract

摘要：

基因组编辑技术的飞速发展,尤其是近年来CRISPR/Cas9基因组编辑体系的出现,使得研究人员能高效地在细胞系和动物模型中对基因组进行精确编辑。基于基因组编辑技术的各种实验研究平台被相继开发,包括通过在细胞系中引入疾病相关突变位点建立疾病模型,通过高通量筛选寻找导致肿瘤耐药性的突变基因,通过体内原位靶向致病基因并修改突变进行基因治疗等。这些基因组编辑技术研究平台极大推动了精准医学研究领域的发展。本文对基因组编辑技术在精准医学领域的基础研究、转化应用、目前存在的问题以及未来发展的方向进行了讨论。

关键词: CRISPR/Cas9, 干细胞疾病模型, 大规模筛选, 基因治疗

Abstract:

The emergence of genome editing tools, such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has enabled researchers to achieve somatic and germline genomic manipulations in cell lines and model organisms. Within a couple of years, genome editing is now being rapidly developed for multiple applications and widely used in biomedical researches, including creation of disease models with desired genetic mutations, screening in a high-throughput manner for drug resistance genes, and making appropriate editions to genes in vivo for disease treatment. All these applications have been facilitating the development of precision medicine research. In this review, we describe the use of genome editing technologies for a variety of research and translational applications in the precision medicine field. We also highlight some of the existing limitations or challenges as well as future directions.

Key words: CRISPR/Cas9, hPSCs disease modeling, high-throughput screening, gene therapy

李爽,杨圆圆,邱艳,陈彦好,徐璐薇,丁秋蓉. 基因组编辑技术在精准医学中的应用[J]. 遗传, 2017, 39(3): 177-188.

Shuang Li,Yuanyuan Yang,Yan Qiu,Yanhao Chen,Luwei Xu,Qiurong Ding. Applications of genome editing tools in precision medicine research[J]. Hereditas(Beijing), 2017, 39(3): 177-188.

参考文献

[1]	Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med, 2015, 372(9): 793-795.
[2]	Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet, 2010, 11(9): 636-646.
[3]	Sun N, Zhao HM. Transcription activator-like effector nucleases (TALENs): a highly efficient and versatile tool for genome editing. Biotechnol Bioeng, 2013, 110(7): 1811-1821.
[4]	Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell, 2014, 157(6): 1262-1278.
[5]	Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, Volz SE, Joung J, van der Oost J, Regev A, Koonin EV, Zhang F. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell, 2015, 163(3): 759-771.
[6]	Fonfara I, Richter H, Bratovi? M, Le Rhun A, Charpentier E. The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA. Nature, 2016, 532(7600): 517-521.
[7]	Abudayyeh OO, Gootenberg JS, Konermann S, Joung J, Slaymaker IM, Cox DBT, Shmakov S, Makarova KS, Semenova E, Minakhin L, Severinov K, Regev A, Lander ES, Koonin EV, Zhang F. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector.. Science, 2016, 353(6299): aaf5573.
[8]	East-Seletsky A, O'Connell MR, Knight SC, Burstein D, Cate JH, Tjian R, Doudna JA. Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. Nature, 2016, 538(7624): 270-273.
[9]	Xu S, Cao SS, Zou BJ, Yue YY, Gu C, Chen X, Wang P, Dong XH, Xiang Z, Li K, Zhu MS, Zhao QS, Zhou GH. An alternative novel tool for DNA editing without target sequence limitation: the structure-guided nuclease. Genome Biol, 2016, 17: 186.
[10]	Burstein D, Harrington LB, Strutt SC, Probst AJ, Anantharaman K, Thomas BC, Doudna JA, Banfield JF. New CRISPR-Cas systems from uncultivated microbes. Nature, 2016, 542(7640): 237-241.
[11]	Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA. Repurposing CRISPR as an RNA- guided platform for sequence-specific control of gene expression. Cell, 2013, 152(5): 1173-1183.
[12]	Gilbert LA, Larson MH, Morsut L, Liu ZR, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell, 2013, 154(2): 442-451.
[13]	Cheng AW, Wang HY, Yang H, Shi LY, Katz Y, Theunissen TW, Rangarajan S, Shivalila CS, Dadon DB, Jaenisch R. Multiplexed activation of endogenous genes by CRISPR- on, an RNA-guided transcriptional activator system. Cell Res, 2013, 23(10)

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基因组编辑技术在精准医学中的应用

Applications of genome editing tools in precision medicine research

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