基于CRISPR/Cas9技术的β-地中海贫血和血友病基因治疗研究进展  

Advances in gene therapy forβ-thalassemia and hemophilia based on the CRISPR/Cas9 technology

作　　者：鲍莉雯 周一叶 曾凡一[1,2] Liwen Bao;Yiye Zhou;Fanyi Zeng(Shanghai Key Laboratory of Embryo and Reproduction Engineering,Key Laboratory of Embryo Molecular Biology of National Health Commission,Shanghai Institute of Medical Genetics,Shanghai Children’s Hospital,Shanghai Jiao Tong University,Shanghai 200040,China;Department of Histoembryology,Genetics&Development,Shanghai Jiao Tong University College of Basic Medical Sciences,Shanghai 200025,China)

机构地区：[1]上海交通大学附属儿童医院,上海市儿童医院,上海交通大学医学遗传研究所,国家卫生健康委员会医学胚胎分子生物学重点实验室,上海市胚胎与生殖工程重点实验室,上海200040 [2]上海交通大学基础医学院组织胚胎学与遗传发育学系,上海200025

出　　处：《遗传》2020年第10期949-964,共16页Hereditas（Beijing)

基　　金：国家重点研发计划(编号:2016YFC1000503);上海市重中之重重点学科项目(编号:2017ZZ02019);上海市临床重点专科项目(编号:shslczdzk05705)。

摘　　要：地中海贫血和血友病是由基因异常引发的常见的遗传性血液病,难以根治且可遗传给下一代,造成严重的家庭和社会负担。基因治疗的出现为遗传性疾病提供了新的治疗方案,但自1990年第1项基因治疗临床试验被批准以来,30年间基因治疗的发展并不乐观。随着基因编辑技术的发展,尤其具有编辑效率高、操作简单、成本低等优势的第三代基因编辑技术CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)的发展,基因编辑介导的基因治疗越来越受到关注,有望根治地中海贫血和血友病等遗传性血液病。本文综述了近6年(2014~2020年)基于CRISPR/Cas9技术的β-地中海贫血和血友病基因治疗基础研究进展,总结了基于CRISPR/Cas9技术的基因治疗临床试验概况,并对CRISPR/Cas9技术用于基因治疗存在的问题和可能的解决方案进行探讨,以期为基于CRISPR/Cas9技术的遗传性血液病基因治疗相关研究提供参考。Thalassemia and hemophilia are common inherited blood disorders caused by genetic abnormalities.These diseases are difficult to cure and can be inherited to the next generation,causing severe family and social burden.The emergence of gene therapy provides a new treatment for genetic diseases.However,since its first clinical trial in 1990,the development of gene therapy has not been as optimistic in the past three decades as one could hope.The development of gene-editing technology,particularly the third generation gene-editing technology CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9),has given hope in such therapeutic approach for having advantages in high editing efficiency,simple operation,and low cost.Gene editing-mediated gene therapy has thus received increasing attention from the biomedical community.It has shown promises for the treatment of inherited blood disorders,such as thalassemia and hemophilia.This paper reviews the fundamental research progress of gene therapy forβ-thalassemia and hemophilia based on CRISPR/Cas9 technology in the past six years.It also summarizes the CRISPR/Cas9-based clinical trials of gene therapy.The problems and possible solutions to this technology for gene therapy are also discussed,thereby providing a reference for the research on gene therapy of inherited blood disorders based on CRISPR/Cas9 technology.

关 键 词：CRISPR/Cas9 基因治疗 遗传性血液病 临床试验 

分 类 号：R554.1[医药卫生—血液循环系统疾病] R556.61[医药卫生—内科学]