上海交通大学学报（医学版）2025，Vol.45Issue(5)：540-548,9.DOI:10.3969/j.issn.1674-8115.2025.05.002
地中海贫血基因治疗研究进展及思考
Research progress and considerations for thalassemia gene therapy
摘要
Abstract
Traditional treatment modalities for thalassemia include regular blood transfusions and allogenic hematopoietic stem cell transplantation(allo-HSCT).In recent years,autologous transplantation of gene-modified hematopoietic stem cells has emerged as a new curative strategy for transfusion-dependent thalassemia(TDT),which has the potential to replace conventional treatments,and provide lifelong benefits for patients.There are two existing technical approaches for gene therapy of β-thalassemia:gene addition,which involves transducing exogenous β-globin genes into hematopoietic stem cells(HSCs),and gene editing,which utilizes CRISPR-Cas9 or other editing systems to re-activate the expression of γ-globin gene.This article summarizes the marketed products and research progress in clinical trials,aiming to analyze the respective advantages and limitations of these two approaches,and discusses the effectiveness and safety of current gene therapies for β-thalassemia,as well as the future directions for associated technologies,including ex vivo HSC expansion with maintenance of stemness and vector-mediated in vivo gene modification.In terms of clinical translational medicine,this article provides in-depth insights into promising solutions for contemporary challenges confronted in clinical trials,including process development challenges,clinical trial conduct,regulatory approval processes,commercialization and payment systems.关键词
地中海贫血/基因治疗/自体造血干细胞移植/基因编辑/转化医学Key words
thalassemia/gene therapy/autologous hematopoietic stem-cell transplantation/gene editing/translational medicine分类
医药卫生引用本文复制引用
高欣洁,刘艳,王大威..地中海贫血基因治疗研究进展及思考[J].上海交通大学学报（医学版）,2025,45(5):540-548,9.基金项目
国家自然科学基金(82450107,82000185) （82450107,82000185）
中央高校基本科研专项资金(YG2022QN013,YG2024QNB02) （YG2022QN013,YG2024QNB02）
中国工程院咨询研究项目(2021-DFY-2). National Natural Science Foundation of China(82450107,82000185) （2021-DFY-2）
Fundamental Research Funds for the Central Universities(YG2022QN013,YG2024QNB02) （YG2022QN013,YG2024QNB02）
Chinese Academy of Engineering Consulting Research Project(2021-DFY-2). （2021-DFY-2）
