陈缘, 陈宇轩, 平渊. 碱基编辑系统在遗传性疾病治疗中的应用J. 药学学报, 2020,55(7): 1562-1572. doi: 10.16438/j.0513-4870.2020-0942
引用本文: 陈缘, 陈宇轩, 平渊. 碱基编辑系统在遗传性疾病治疗中的应用J. 药学学报, 2020,55(7): 1562-1572. doi: 10.16438/j.0513-4870.2020-0942
CHEN Yuan, CHEN Yu-xuan, PING Yuan. Application of base editors in the treatment of genetic disordersJ. Acta Pharmaceutica Sinica, 2020,55(7): 1562-1572. doi: 10.16438/j.0513-4870.2020-0942
Citation: CHEN Yuan, CHEN Yu-xuan, PING Yuan. Application of base editors in the treatment of genetic disordersJ. Acta Pharmaceutica Sinica, 2020,55(7): 1562-1572. doi: 10.16438/j.0513-4870.2020-0942

碱基编辑系统在遗传性疾病治疗中的应用

Application of base editors in the treatment of genetic disorders

  • 摘要: CRISPR/Cas系统是现阶段应用最广泛的基因组编辑工具,但由于其激活同源重组进行DNA修复的效率低且存在脱靶效应,严重限制了该工具在基因治疗方面的应用。碱基编辑是一种基于CRISPR/Cas系统的基因编辑新策略,其工作原理是利用其结合的碱基脱氨酶精确编辑目标DNA或RNA上一小段窗口内的核苷酸。碱基编辑系统包括胞嘧啶碱基编辑系统(CBEs)和腺嘌呤碱基编辑系统(ABEs),可以分别实现碱基对C·G到T·A和A·T到G·C的转换。碱基编辑系统作用过程中不依赖于DNA双链断裂的发生,无需引入供体DNA,并因其高效性及特异性已被广泛应用于遗传性疾病治疗的研究中。本文综述了近年来碱基编辑系统的发展历程和在遗传性疾病治疗中的潜力,并对其作为基因治疗药物的发展前景进行了展望。

     

    Abstract: To date, CRISPR/Cas systems represent the most widely used tool for genome editing; however, its application scope for gene therapy has been largely limited due to its limited efficiency in activating homologydirected repair for DNA and off-target effect. Base editing is a new CRISPR/Cas-based genome-editing strategy, which allows single nucleotide to be precisely corrected in a narrow window scope on the target DNA or RNA by taking advantage of different nucleobase deaminases. Base editors include cytosine base editors (CBEs) and adenine base editors (ABEs), which can induce the conversions from C�G to T�A and A�T to G�C, respectively. Base editors work independently of double-strand DNA breaks (DSBs) and DNA donor templates, and thus they are extensively adopted for a wide range of therapeutic applications for genetic diseases, largely owing to their high efficiency and great specificity. In this review, we summarize the development of base editors and their potentials as therapeutic drugs for treating genetic diseases, and future outlooks are also discussed.

     

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