重组腺相关病毒基因药物临床前评价方法的回顾与展望  

Assessment and Prospects of Preclinical Evaluation Methods of Recombinant Adeno-Associated Virus Gene Medicine

作　　者：李佳莘 黎玲 黄艺峰 刁勇[1] LI Jiashen;LI Ling;HUANG Yifeng;DIAO Yong(School of Medicine,Huaqiao University,Quanzhou 362021,China;Haixia Hospital Affiliated to Huaqiao University,Quanzhou 362000,China)

机构地区：[1]华侨大学医学院,福建泉州362021 [2]华侨大学附属海峡医院,福建泉州362000

出　　处：《华侨大学学报（自然科学版）》2023年第4期421-426,共6页Journal of Huaqiao University(Natural Science)

基　　金：国家自然科学基金资助项目(81371669,81271691,30973591);福建省泉州市科技计划项目(2022C 006R)。

摘　　要：重组腺相关病毒(rAAV)基因药物在临床应用过程中长期疗效不确定,甚至存在安全性风险,是制约其广泛应用的主要障碍.对现有rAAV基因药物临床前评价方法进行分析和梳理.结果表明:仅进行药效学评价不能揭示rAAV转导的细胞和分子机制,而基于转导过程分析的物理转导与功能转导评价存在结果不一致,不能反映rAAV转导的细胞异质性和靶细胞的空间分布特征等问题,难以准确预测rAAV基因药物的临床疗效和安全性,需要从单分子、单细胞水平开展rAAV载体胞内命运评价的新方法,以切实保障新型rAAV基因药物的临床有效性和安全性.Long-term efficacy uncertainty and safety risks of recombinant adeno-associated virus(rAAV)gene medicine in clinical application are the main obstacles restricting their wide applications.The current preclinical evaluation methods for rAAV gene medicine are analyzed and carded.The results show that pharmacodynamic evaluation alone cannot reveal the cellular and molecular mechanisms of rAAV transduction,while physical and functional transduction evaluations based on transduction process analysis have inconsistent results and cannot reveal the cellular heterogeneity and spatial distribution characteristics of target cell of rAAV transduction,making it difficult to accurately predict the clinical efficacy and safety of rAAV gene medicine.It is necessary to construct a new method for evaluating intracellular fate of rAAV vectors at single-molecule and single-cell level to effectively ensure the clinical efficacy and safety of novel rAAV gene medicine.

关 键 词：基因治疗 临床前评价 胞内命运 重组腺相关病毒 

分 类 号：R394[医药卫生—医学遗传学]