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CRISPR/Cas9基因编辑技术在妇科恶性肿瘤研究及治疗中应用的进展

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Author:: No author available

Journal Title:: Chinese Journal of Obstetrics and Gynecology

Issue:: 1

DOI:: 10.3760/cma.j.issn.0529-567x.2018.01.016

Key Word:: No keyword available

Abstract：恶性肿瘤是1种进化过程的衍生物,达尔文的选择进化理论揭示了恶性肿瘤是物种在进化过程中遗传突变逐步累积的结果.每种恶性肿瘤都是由许多复杂的克隆细胞亚群组成的,这些亚群决定了特定人群在特定阶段存在特定的肿瘤基因型和表型,这种肿瘤内的异质性对于恶性肿瘤的进展、转移以及化疗耐药有着显著影响[1].目前,妇科恶性肿瘤的主要治疗方式仍然是以手术为主辅以放化疗的综合治疗,化疗耐药是影响患者预后的重要因素,耐药的主要原因是耐药相关基因的异常表达,因此,靶向妇科恶性肿瘤显著突变的致病基因和耐药基因是未来临床治疗的关键.目前,靶向基因编辑技术已经成为研究肿瘤基因功能和通过校正缺陷基因或引入修饰基因治疗肿瘤的强有力的工具.基因编辑技术主要包括锌指核酸内切酶(zinc finger endonuclease,ZFN)、类转录激活因子效应物核酸酶(transcription activator-like effector nuclease,TALEN)、规律成簇间隔短回文重复(clustered regularly interspaced short palindromic repeat ,CRISPR )/CRISPR 相关蛋白核酸酶( CRISPR-associated nuclease,Cas)9、TargeTron基因敲除系统(the targetron gene knockout system)[2]以及传统的RNA干扰(RNAi)技术[3].与ZFN、TALEN及TargeTron基因敲除系统相比,基于CRISPR/Cas系统的基因编辑技术(即CRISPR/Cas9基因编辑技术)易于操作,效率高,更易得到纯合子突变体,而且可以在不同的位点同时引入多个突变;但因CRISPR系统面临脱靶危机,故其精确度较低.因此,采用CRISPR/Cas9基因编辑技术能高效控制肿瘤细胞内基因的表达水平,进一步从多方面推进肿瘤的研究和应用.肿瘤基因计划的实施和CRISPR/Cas9基因编辑技术的发展,使妇科恶性肿瘤的精准医疗成为可能.本文对近年来CRISPR/Cas9基因编辑技术在妇科恶性肿瘤研究及治疗中的应用进行综述.

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