Research progress and considerations for thalassemia gene therapy
10.3969/j.issn.1674-8115.2025.05.002
- VernacularTitle:地中海贫血基因治疗研究进展及思考
- Author:
Xinjie GAO
1
;
Yan LIU
1
;
Dawei WANG
1
Author Information
1. 上海血液学研究所,组学与疾病全国重点实验室,国家转化医学研究中心(上海),上海交通大学医学院附属瑞金医院,上海 200025
- Publication Type:Journal Article
- Keywords:
thalassemia;
gene therapy;
autologous hematopoietic stem-cell transplantation;
gene editing;
translational medicine
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2025;45(5):540-548
- CountryChina
- Language:Chinese
-
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.
