血友病基因治疗国内外研究新进展

doi:10.3969/j.issn.1000-8535.2024.04.001

广州医药 ›› 2024, Vol. 55 ›› Issue (4): 331-341.DOI: 10.3969/j.issn.1000-8535.2024.04.001

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血友病基因治疗国内外研究新进展

李儒雅¹, 梁亮¹, 周睿卿², 郝嘉懿¹, 阎文锦³, 黄金棋², 王顺清²

1 广东医科大学附属医院血液内科（广东湛江 524000）
2 广州市第一人民医院血液内科（广东广州 510180）
3 兰州大学基础医学院（甘肃兰州 730000）

出版日期:2024-04-20 发布日期:2024-05-17
通讯作者: 黄金棋,E-mail：Eyhjq@scut.edu.cn;王顺清,E-mail：shqwang_cn@163.com
作者简介:王顺清医学博士，主任医师，博士生导师。广州市第一人民医院（华南理工大学附属二院）内科兼血液内科主任，中国医师协会血液科医师分会委员，中华医学会血液学分会红细胞疾病学组委员，广东省医学会血液病学分会副主任委员，广州市医学会血液学分会主任委员等。从事血液病学临床、教学和科研工作30余年，主要研究方向是再生障碍性贫血诊治、造血干细胞移植以及细胞治疗和基因治疗。主持和参与国家重点研发计划、国家自然科学基金以及省市各级科研项目20余项，发表论文100余篇，其中SCI收录70余篇，获省市成果6项，专利7项。黄金棋医学博士，美国斯克利普斯研究所（TSRI）联培化学生物学博士，海外留学归国人才，广东省珠江学者内科学设岗专家，欧洲细胞与基因治疗学会（ESCGT）委员，副主任医师，博后导师。主要研究方向是基于多模态深度学习的血液病诊疗新技术开发；主持国自然面上项目以及省部级等课题7项，参与中俄、中美等国际间合作项目3项；是国内首批CAR-T治疗白血病、淋巴瘤等技术的设计者之一，在广东省通过基因治疗技术成功治愈首例输血依赖性重型β-地中海贫血；同时在再生障碍性贫血的神经免疫发病机制，CDR3为靶点的多发性骨髓瘤、淋巴瘤等精准免疫调控技术等领域也有一定涉及。目前已完成发明专利3项，研究成果转化3项，获批临床新药IND批件（CXSL2300699）1项，主持研究者发起临床研究（IIT）2项，WHO中国临床试验中心注册项目3项，ClinicalTrials注册项目2项，并以第一或通讯作者发表LEUKEMIA等SCI论文20余篇。
基金资助:
国家自然科学基金（82270143）; 广东省基础与应用基础研究基金（2022A1515220122）; 湛江市科技计划项目（2022A01019）

Recent advancements in gene therapy for hemophilia

LI Ruya¹, LIANG Liang¹, ZHOU Ruiqing², HAO Jiayi¹, YAN Wenjin³, HUANG Jinqi², WANG Shunqing²

1 Department of Hematology,Affiliated Hospital of Guangdong Medical University（GDMU）,Zhanjiang 524000,China
2 Department of Hematology,Guangzhou First People's Hospital,South China University of Technology,Guangzhou 510180,China
3 School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China

Online:2024-04-20 Published:2024-05-17

摘要/Abstract

摘要： 血友病是一种由于X染色体上凝血因子基因突变所致的遗传性出血性疾病,目前主要的治疗方法是凝血因子替代疗法。但长期频繁的注射用药往往导致患者依从性差,容易产生抑制性抗体,从而影响治疗效果。虽然现在延长半衰期的新型凝血因子药物、人源化双特异性抗体以及抗组织因子途径抑制剂单克隆抗体等用于疾病治疗,在给药方式和作用持续时间上已有很大进步,但它们仍无法治愈血友病。因此,以疾病根治为重要目标的基因治疗被设计出来,近年来受到了广泛的关注。该文介绍了血友病基因治疗的原理、基因治疗载体的选择、基因治疗预处理方案,总结了现阶段基因治疗临床应用的安全性和有效性;最后讨论基因治疗目前存在的问题以及未来发展方向。

关键词: 血友病, 基因治疗, 预处理方案, 临床进展, 存在问题

Abstract: Hemophilia is a genetic bleeding disorder resulting from mutations in coagulation factor genes on the X chromosome．The mainstay of current treatment is coagulation factor replacement therapy．However,frequent and long-term injections often lead to poor patient compliance,easy inhibitor development,and compromised therapeutic efficacy．Despite advancements in delivery methods and prolonged action of novel agents such as extended half-life coagulation factor concentrates,humanized bispecific antibodies,and anti-tissue factor pathway inhibitor monoclonal antibodies,these approaches still fall short of curing hemophilia．Consequently,gene therapy,aiming for disease eradication,has garnered significant attention in recent years．This review delves into the principles of gene therapy,the selection of gene therapy vectors,and gene therapy preconditioning regimens．It summarizes the safety and efficacy of gene therapy in current clinical applications and discusses challenges and future directions in this field．

Key words: hemophilia, gene therapy, conditioning, clinical advancements, challenges

李儒雅, 梁亮, 周睿卿, 郝嘉懿, 阎文锦, 黄金棋, 王顺清. 血友病基因治疗国内外研究新进展[J]. 广州医药, 2024, 55(4): 331-341.

LI Ruya, LIANG Liang, ZHOU Ruiqing, HAO Jiayi, YAN Wenjin, HUANG Jinqi, WANG Shunqing. Recent advancements in gene therapy for hemophilia[J]. Guangzhou Medical Journal, 2024, 55(4): 331-341.

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血友病基因治疗国内外研究新进展

Recent advancements in gene therapy for hemophilia

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