CRISPR/Cas9基因组编辑技术在HIV-1感染治疗中的应用进展

doi:10.16288/j.yczz.15-284

遗传 ›› 2016, Vol. 38 ›› Issue (1): 9-16.doi: 10.16288/j.yczz.15-284

CRISPR/Cas9基因组编辑技术在HIV-1感染治疗中的应用进展

韩英伦^{1, 2}, 李庆伟^{1, 2}

1. 辽宁师范大学生命科学学院,大连 116029;
2. 辽宁师范大学七鳃鳗研究中心,大连 116029

收稿日期:2015-06-19 修回日期:2015-09-07 出版日期:2016-01-20 发布日期:2016-01-20
通讯作者: 李庆伟,教授,博士生导师,研究方向：细胞生物学。E-mail: liqw@263.net E-mail:hanyinglun@163.com
作者简介:韩英伦,讲师,研究方向：细胞生物学。
基金资助:
国家重点基础研究发展规划(973计划)(编号：2013CB835304),全国海洋公益项目(编号：201305016),国家自然科学基金项目(编号：31170353, 31202020, 31271323)和大连市科技计划(编号：2013E11SF056)资助

Application progress of CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection

Yinglun Han^{1, 2}, Qingwei Li^{1, 2}

1. College of Life Science, Liaoning Normal University, Dalian 116029, China;
2. Lamprey Research Center, Liaoning Normal University, Dalian 116029, China

Received:2015-06-19 Revised:2015-09-07 Online:2016-01-20 Published:2016-01-20
Supported by:
[Supported by grants from the National Program on Key Basic Research Project (973 Program) (No; 2013CB835304), the National Marine Public Projects (No; 201305016), the National Natural Science Foundation of China (General Program) (Nos; 31170353, 31202020, 31271323), and Dalian Science and Technology Program (No; 2013E11SF056)]

摘要/Abstract

摘要： 基因治疗是将外源正常基因通过一定方式导入人体靶细胞以纠正或补偿因基因缺陷和异常引起的疾病,从而达到治疗目的。因此,基因治疗的技术方法在研究持续感染HIV-1或潜伏感染HIV-1原病毒患者的治疗中具有重大的现实意义。目前,现有的基因治疗方法存在识别靶向位点有限及脱靶几率大等主要问题。最新研究表明来源于细菌和古菌的规律间隔成簇短回文重复序列及其相关核酸酶9系统[Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9), CRISPR/Cas9]已被成功改造成基因组定点编辑工具。因此,如何利用CRISPR/Cas9系统实现对HIV-1病毒基因组进行高效靶向修饰,从而达到治疗HIV-1感染病患的目的已经成为当前研究的热点。本文参考最新国内外研究成果,重点介绍了 CRISPR/Cas9基因组编辑技术在HIV-1感染疾病治疗中的应用,主要包括CCR5基因编辑、清除HIV-1原病毒以及活化HIV-1原病毒,以期为HIV-1感染疾病的预防与治疗提供重要研究参考。

关键词: CRISPR/Cas9, 人类免疫缺陷病毒, 基因组编辑

Abstract: The goal of gene therapy is to introduce foreign genes into human target cells in a certain way to correct or compensate diseases caused by defective or abnormal genes. Therefore, gene therapy has great practical significance in studying the treatment of persistent or latent HIV-1 infection. At present, the existing methods of gene therapy have some major defects such as limited target site recognition and high frequency of off-targets. The latest research showed that the clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR-associated nuclease 9 (Cas9) system from bacteria and archaea has been successfully reformed to a targeted genome editing tool. Thus, how to achieve the goal of treating HIV-1 infection by modifying targeted HIV-1 virus genome effectively using the CRISPR/Cas9 system has become a current research focus. Here we review the latest achievements worldwide and briefly introduce applications of the CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection, including CCR5 gene editing, removal of HIV-1 virus and activation of HIV-1 virus, in order to provide reference for the prevention and treatment of HIV-1 infection.

Key words: CRISPR /Cas9, Human immunodeficiency virus, genome editing

韩英伦, 李庆伟. CRISPR/Cas9基因组编辑技术在HIV-1感染治疗中的应用进展[J]. 遗传, 2016, 38(1): 9-16.

Yinglun Han, Qingwei Li. Application progress of CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection[J]. HEREDITAS(Beijing), 2016, 38(1): 9-16.

参考文献

[1] Saayman S, Ali SA, Morris KV, Weinberg MS. The therapeutic application of CRISPR/Cas9 technologies for HIV. Expert Opin Biol Ther , 2015, 15(6): 819-830.
[2] Yin LJ, Hu SQ, Guo F. The application of CRISPR-Cas9 gene editing technology in viral infection diseases. Hereditas(Beijing) , 2015, 37(5): 412-418. 殷利眷, 胡斯奇, 郭斐. CRISPR-Cas9基因编辑技术在病毒感染疾病治疗中的应用. 遗传, 2015, 37(5): 412-418.
[3] Gaj T, Gersbach CA, Barbas III CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol , 2013, 31(7): 397-405.
[4] Cai M, Yang Y. Targeted genome editing tools for disease modeling and gene therapy. Curr Gene Ther , 2014, 14(1): 2-9.
[5] DiGiusto DL, Krishnan A, Li LJ, Li HT, Li S, Rao A, Mi S, Yam P, Stinson S, Kalos M, Alvarnas J, Lacey SF, Yee JK, Li MJ, Couture L, Hsu D, Forman SJ, Rossi JJ, Zaia JA. RNA-based gene therapy for HIV with lentiviral vector-modified CD34 + cells in patients undergoing transplantation for AIDS-related lymphoma. Sci Transl Med , 2010, 2(36): 36RA43.
[6] Hao YZ, Teng ZP, Zeng Y. HIV gene therapy overview and the latest developments. Chinese J Exp Clin Virol , 2013, 27(2): 156-158. 郝彦哲, 滕智平, 曾毅. HIV基因治疗概况及最新进展. 中华实验和临床病毒学杂志, 2013, 27(2): 156-158.
[7] Tian YR, Jiao YM, Zhang T, Wu H. Recent progress in the gene therapies against HIV-1. J Cap Med Univ , 2014, 35(1): 101-107. 田雅茹, 焦艳梅, 张彤, 吴昊. 抗HIV-1基因治疗新进展. 首都医科大学学报, 2014, 35(1): 101-107.
[8] Chung J, Scherer LJ, Gu A, Gardner AM, Torres-Coronado M, Epps EW, DiGiusto DL, Rossi JJ. Optimized lentiviral vectors for HIV gene therapy: multiplexed expression of small RNAs and inclusion of MGMT P140K drug resistance gene. Mol Ther , 2014, 22(5): 952-963.
[9] Mojica FJ, Díez-Villaseñor C, García-Martínez J, Almendros C. Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiology , 2009, 155(Pt 3): 733-740.
[10] Mojica FJM, Díez-Villaseñor C, García-Martínez J, Soria E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol , 2005, 60(2): 174-182.
[11] Strong CL, Guerra HP, Mathew KR, Roy N, Simpson LR, Schiller MR. Damaging the integrated HIV proviral DNA with TALENs. PLoS One , 2015, 10(5): e0125652.
[12] Ye L, Wang JM, Beyer AI, Teque F, Cradick TJ, Qi ZX, Chang JC, Bao G, Muench MO, Yu JW, Levy JA, Kan YW. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection. Proc Natl Acad Sci USA , 2014, 111(26): 9591-9596.
[13] Yi G, Choi JG, Bharaj P, Abraham S, Dang Y, Kafri T, Alozie O, Manjunath MN, Shankar P. CCR5 gene editing of resting CD4 + T cells by transient ZFN expression from HIV envelope pseudotyped nonintegrating lentivirus confers HIV-1 resistance in humanized mice. Mol Ther Nucleic Acids , 2014, 3: e198.
[14] Ru RN, Yao YC, Yu SL, Yin BP, Xu WW, Zhao ST, Qin L, Chen XP. Targeted genome engineering in human induced pluripotent stem cells by penetrating TALENs. Cell Regen (Lond) , 2013, 2(1): 5.
[15] Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science , 2012, 337(6096): 816-821.
[16] Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, Hsu PD, Wu XB, Jiang WY, Marraffini LA, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science , 2013, 339(6121): 819-823.
[17] Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J. RNA-programmed genome editing in human cells. Elife , 2013, 2: e00471.
[18] Mali P, Yang LH, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. RNA-guided human genome engineering via Cas9. Science , 2013, 339(6121): 823-826.
[19] Gilbert LA, Larson MH, Morsut L, Liu ZR, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weiss

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CRISPR/Cas9基因组编辑技术在HIV-1感染治疗中的应用进展

Application progress of CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection

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