血友病基因治疗国内外研究新进展  

Recent advancements in gene therapy for hemophilia

作　　者：李儒雅 梁亮 周睿卿[2] 郝嘉懿 阎文锦 黄金棋 王顺清[2] LI Ruya;LIANG Liang;ZHOU Ruiqing;HAO Jiayi;YAN Wenjin;HUANG Jinqi;WANG Shunqing(Department of Hematology,Affiliated Hospital of Guangdong Medical University(GDMU),Zhanjiang 524000,China;Department of Hematology,Guangzhou First People’s Hospital,South China University of Technology,Guangzhou 510180,China;School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China)

机构地区：[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　　处：《广州医药》2024年第4期331-341,359,共12页Guangzhou Medical Journal

基　　金：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)

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。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.

关 键 词：血友病 基因治疗 预处理方案 临床进展 存在问题 

分 类 号：R73[医药卫生—肿瘤]