腺相关病毒载体基因治疗药物生物分析技术及药代/药效动力学研究进展  

Advances in Bioanalytical Techniques and Pharmacokinetics/Pharmacodynamics Research of Adeno-Associated Viral Vector Gene Therapy Drugs

作　　者：任建伟 郑昕 韩晓红 REN Jianwei;ZHENG Xin;HAN Xiaohong(Clinical Pharmacology Research Center,Peking Union Medical College Hospital,State Key Laboratory of Complex Severe and Rare Diseases,NMPA Key Laboratory for Clinical Research and Evaluation of Drug,Beijing Key Laboratory of Clinical PK&PD Investigation for Innovative Drugs,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院临床药理研究中心、疑难重症及罕见病全国重点实验室、国家药监局药物临床研究与评价重点实验室、创新药物临床PK/PD北京市重点实验室,北京100730

出　　处：《罕见病研究》2024年第3期350-357,共8页Journal of Rare Diseases

基　　金：中国医学科学院医学与健康科技创新工程(2021-I2M-1-003);中央高水平医院临床科研业务费(2022-PUMCH-B-033)。

摘　　要：腺相关病毒(AAV)载体是近年来基因治疗领域的研究热点,由于其致病能力弱、免疫原性低、组织特异性强等特点,在基因治疗领域展现出了极大的潜力。AAV载体本质上为具有感染活性的病毒,其安全性和有效性需要新的生物分析技术来评估。目前,相关行业指南明确了对AAV载体生物分布、脱落、免疫原性等内容的评估需求,但对生物分析相关的要求却十分有限。本文从生物分布、脱落、免疫原性和药代动力学/药效动力学(PK/PD)研究4个方面对AAV载体基因治疗药物生物分析技术及PK/PD研究面临的挑战进行总结,以期为AAV载体基因治疗产品的临床研发提供参考。Recently,adeno-associated virus(AAV)vectors have been a hotspot in gene therapy and have shown great potential for rare diseases therapy,due to their low pathogenicity,mild immunogenicity and high tissue specificity.The safety and efficacy of AAV vectors,which are essentially infectious viruses,require new bioanalytical techniques to assess.At present,the relevant industry guidelines have specified the needs for the assessment of biodistribution,shedding,and immunogenicity,but the requirements related to bioassay are limited.In this paper,we reviewed the bioanalytical techniques and pharmacokinetics/pharmacodynamics(PK/PD)research of AAV vectors and their challenges from four aspects:biodistribution,shedding,immunogenicity and PK/PD research,with the hope of providing some reference for the clinical development of AAV vectors gene therapy products.

关 键 词：腺相关病毒 生物分析 基因治疗 生物分布 脱落 

分 类 号：R95[医药卫生—药学]