基因编辑造血干祖细胞的研究进展  

Gene Editing of Hematopoietic Stem and Progenitor Cells

作　　者：温伟 施均 张健萍 程涛 张孝兵 WEN Wei;SHI Jun;ZHANG Jianping;CHENG Tao;ZHANG Xiaobing(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津300020

出　　处：《中国细胞生物学学报》2022年第1期175-184,共10页Chinese Journal of Cell Biology

基　　金：中国医学科学院医学与健康科技创新工程项目(批准号:2021-I2M-1-041)资助的课题。

摘　　要：基因编辑技术的飞速发展给造血干祖细胞基因治疗带来了新的机遇。CRISPR-Cas9等技术能够实现特定基因的定向编辑。基因编辑技术的不断优化使编辑效率显著提高,检测技术的进步也促进了对基因编辑细胞安全性的评估,包括检测脱靶效应和大片段删除突变。造血干祖细胞基因编辑已经进入临床试验阶段,但是目前的编辑技术可能会影响细胞功能和基因组稳定性,在临床应用中应当引起注意。这篇综述总结了基因编辑的技术原理、基因编辑技术在造血干祖细胞中的应用和基因治疗研究,并探讨了基因编辑产品的安全性提升方法和质控方案。The rapid development of gene-editing technologies has opened new opportunities for HSPC(hematopoietic stem and progenitor cell)gene therapies.Gene editing techniques such as CRISPR-Cas9 enable precise modifications at desired gene sites.Currently,it can achieve high on-target editing efficiencies,whereas there are also safety concerns,such as off-target effects and large-deletion mutations.Clinical trials have demonstrated the potential of HSPC gene editing therapies.However,the impairment of HSPC function and genomic integrity after editing deserves attention.This review summarizes the principle of gene editing,the basic and clinical advances in gene editing of HSPC.Furthermore,it also discusses putative strategies to improve the safety profiles of gene editing products and establish feasible quality control processes.

关 键 词：CRISPR-Cas9 基因编辑 造血干祖细胞 同源重组 地中海贫血 造血干细胞移植 基因治疗 

分 类 号：Q78[生物学—分子生物学]