Site-specific genome editing in treatment of inherited diseases:possibility,progress,and perspectives

作     者：Chao Huang Qing Li Jinsong Li Chao Huang;Qing Li;Jinsong Li

作者机构：Key Laboratory of Systems Health Science of Zhejiang ProvinceSchool of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesNo.1 Sub-Lane XiangshanHangzhou 310024ZhejiangChina State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesNo.320 Yueyang RoadShanghai 200031China Key Laboratory of Systems Health Science of Zhejiang ProvinceSchool of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiangChina State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina 

出 版 物：《Medical Review》 (医学评论（英文）)

年 卷 期：2022年第2卷第5期

页      面：471-500页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Genome Tagging Project and grants from the National Natural Science Foundation of China(31821004,32030029,31730062,and 3210060158) CAS Special Research Assistant Program. 

主　　题：clinical applications genome editing inherited diseases mutations principles. 

摘      要：Advancements in genome editing enable permanent changes of DNA sequences in a site-specific manner,providing promising approaches for treating human genetic disorders caused by gene mutations.Recently,genome editing has been applied and achieved significant progress in treating inherited genetic disorders that remain incurable by conventional therapy.Here,we present a review of various programmable genome editing systems with their principles,advantages,and limitations.We introduce their recent applications for treating inherited diseases in the clinic,including sickle cell disease(SCD),β-thalassemia,Leber congenital amaurosis(LCA),heterozygous familial hypercholesterolemia(HeFH),etc.We also discuss the paradigm of ex vivo and in vivo editing and highlight the promise of somatic editing and the challenge of germline editing.Finally,we propose future directions in delivery,cutting,and repairing to improve the scope of clinical applications.