CRISPR/Cas9基因编辑技术及其在肿瘤治疗中的应用

国际肿瘤学杂志››2018,Vol. 45››Issue (8): 556-560.doi:10.3760/cma.j.issn.1673-422X.2018.09.010

CRISPR/Cas9基因编辑技术及其在肿瘤治疗中的应用

杨业环，杨成玮，谭小庆，高兴春

710021 西安医学院基础医学部陕西省脑疾病防治重点实验室

出版日期:2018-09-08发布日期:2018-11-15
通讯作者:高兴春 E-mail:gxc199281003@163.com
基金资助:

国家自然科学基金（81873740）；陕西省自然科学基金（2017JM8086）；西安医学院分子免疫学重点学科；陕西省优势学科建设经费资助项目；大学生创新创业训练计划项目(G201711840017)

CRISPR/Cas9 genome editing system and its application in tumor therapy

Yang Yehuan, Yang Chengwei, Tan Xiaoqing, Gao Xingchun

Institute of Basic Medical Sciences, Xi′an Medical University; Shaanxi Key Laboratory of Brain Disorders, Xi′an 710021, China

Online:2018-09-08Published:2018-11-15
Contact:Gao Xingchun E-mail:gxc199281003@163.com
Supported by:

National Natural Science Foundation of China (81873740); Natural Science Foundation of Shaanxi Province of China (2017JM8086); Xi′an Medical University′s Key Disciplines of Molecular Immunology; Leading Disciplines Development Government Foundation of Shaanxi Province; College Students′ Innovation and Entrepreneurship Training Program (G201711840017)

摘要/Abstract

摘要：CRISPR/Cas9基因编辑系统是在古细菌抵御外源核酸入侵的免疫机制基础上人工改造而成的一种新型基因编辑技术。由于其高效率和准确性，CRISPR/Cas9基因编辑技术已经广泛应用于肿瘤治疗的研究中，如靶向敲除致癌基因、修复抑癌基因、打破免疫耐受、构建肿瘤模型等，为肿瘤基因治疗带来革命性的发展。

杨业环，杨成玮，谭小庆，高兴春. CRISPR/Cas9基因编辑技术及其在肿瘤治疗中的应用[J]. 国际肿瘤学杂志, 2018, 45(8): 556-560.

Yang Yehuan, Yang Chengwei, Tan Xiaoqing, Gao Xingchun. CRISPR/Cas9 genome editing system and its application in tumor therapy[J]. Journal of International Oncology, 2018, 45(8): 556-560.

［1］ Ul Ain Q, Chung JY, Kim YH. Current and future delivery systems for engineered nucleases: ZFN, TALEN and RGEN［J］. J Control Release, 2015, 205: 120127. DOI: 10.1016/j.jconrel.2014.12.036. ［2］ Mojica FJ, DiezVillasenor C, Soria E, et al. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria［J］. Mol Microbiol, 2000, 36(1): 244246. ［3］ Barrangou R, Fremaux C, Deveau H, et al. CRISPR provides acquired resistance against viruses in prokaryotes［J］. Science, 2007, 315(5819): 17091712. DOI: 10.1126/science.1138140. ［4］ Mojica FJ, DiezVillasenor C, GarciaMartinez J, et al. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements［J］. J Mol Evol, 2005, 60(2): 174182. DOI: 10.1007/s0023900400463. ［5］ Brouns SJ, Jore MM, Lundgren M, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes［J］. Science, 2008, 321(5891): 960964. DOI: 10.1126/science.1159689. ［6］ Marraffini LA, Sontheimer EJ. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA［J］. Science, 2008, 322(5909): 18431845. DOI: 10.1126/science.1165771. ［7］ Deveau H, Barrangou R, Garneau JE, et al. Phage response to CRISPRencoded resistance in Streptococcus thermophilus［J］. J Bacteriol, 2008, 190(4): 13901400. DOI: 10.1128/JB.0141207. ［8］ Shen J, Lv L, Wang X, et al. Comparative analysis of CRISPRCas systems in Klebsiella genomes［J］. J Basic Microbiol, 2017, 57(4): 325336. DOI: 10.1002/jobm.201600589. ［9］ Guan L, Han Y, Zhu S, et al. Application of CRISPRCas system in gene therapy: preclinical progress in animal model［J］. DNA Repair (Amst), 2016, 46: 18. DOI: 10.1016/j.dnarep.2016.07.004. ［10］ Makarova KS, Wolf YI, Alkhnbashi OS, et al. An updated evolutionary classification of CRISPRCas systems［J］. Nat Rev Microbiol, 2015, 13(11): 722736. DOI: 10.1038/nrmicro3569. ［11］杨帆, 李寅. 新一代基因组编辑系统CRISPR/Cpf1［J］. 生物工程学报, 2017, 33(3): 361371. DOI: 10.13345/j.cjb.170029. ［12］ Kunin V, Sorek R, Hugenholtz P. Evolutionary conservation of sequence and secondary structures in CRISPR repeats［J］. Genome Biol, 2007, 8(4): R61. DOI: 10.1186/gb200784r61. ［13］ Barrangou R, Fremaux C, Deveau H, et al. CRISPR provides acquired resistance against viruses in prokaryotes［J］. Science, 2007, 315(5819): 17091712. DOI: 10.1126/science.1138140. ［14］杨悦, 訾晓渊, 孙颖浩. CRISPRCas基因编辑技术在泌尿系统肿瘤研究中的应用［J］. 中国肿瘤生物治疗杂志, 2018, 25(1): 916. DOI: 10.3872/j.issn.1007385X.2018.01.002. ［15］ Li Y, Ma S, Sun L, et al. Programmable single and multiplex baseediting in bombyx mori using RNAguided cytidine deaminases［J］. G3 (Bethesda), 2018, 8(5): 17011709. DOI: 10.1534/g3.118.200134. ［16］ White MK, Khalili K. CRISPR/Cas9 and cancer targets: future possibilities and present challenges［J］. Oncotarget, 2016, 7(11): 1230512317. DOI: 10.18632/oncotarget.7104. ［17］孟泽松, 王飞飞, 王光林, 等. CRISPR/Cas9基因编辑技术在肿瘤研究及治疗中的应用［J］. 肿瘤, 2016, 36(5): 13951401. DOI: 10.3781/j.issn.10007431.2016.55.514. ［18］ Hu Z, Yu L, Zhu D, et al. Disruption of HPV16E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells［J］. Biomed Res Int, 2014, 2014: 612823. DOI: 10.1155/2014/612823. ［19］ Zhen S, Li X. Oncogenic human papillomavirus: application of CRISPR/Cas9 therapeutic strategies for cervical cancer［J］. Cell Physiol Biochem, 2017, 44(6): 24552466. DOI: 10.1159/000486168. ［20］ Noguchi T, Ward JP, Gubin MM, et al. Temporally distinct PDL1 expression by tumor and host cells contributes to immune escape［J］. Cancer Immunol Res, 2017, 5(2): 106117. DOI: 10.1158/23266066.CIR160391. ［21］ Su S, Hu B, Shao J, et al. CRISPRCas9 mediated efficient PD1 disruption on human primary T cells from cancer patients［J］. Sci Rep, 2016, 6: 20070. DOI: 10.1038/srep20070. ［22］ Kalebic N, Taverna E, Tavano S, et al. CRISPR/Cas9induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo［J］. EMBO Rep, 2016, 17(3): 338348. DOI: 10.15252/embr.201541715. ［23］ Li L, Hu S, Chen X. Nonviral delivery systems for CRISPR/Cas9based genome editing: challenges and opportunities［J］. Biomaterials, 2018, 171: 207218. DOI: 10.1016/j.biomaterials.2018.04.031. ［24］ Kulcsár PI, Tálas A, Huszár K, et al. Crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage［J］. Genome Biol, 2017, 18(1): 190. DOI: 10.1186/s1305901713188. ［25］ Chen JS, Dagdas YS, Kleinstiver BP, et al. Enhanced proofreading governs CRISPRCas9 targeting accuracy［J］. Nature, 2017, 550(7676): 407410. DOI: 10.1038/nature24268. ［26］ Cox DBT, Gootenberg JS, Abudayyeh OO, et al. RNA editing with CRISPRCas13［J］. Science, 2017, 358(6366): 10191027. DOI: 10.1126/science.aaq0180.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲.血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊.局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华.Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青.血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺.PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云.新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚.EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵.抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六.基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六.肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东.ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅.基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳.炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝.癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志.宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.