在降低rAAV基因药物免疫反应中减少载体剂量并保持高效表达和药效的实施策略  

Strategy for keeping efficient expression and pharmacodynamics in reducing rAAV gene medicine immune response based on the decrease of vector dosage

作　　者：张国海[1] 曾淑兰[2] 许瑞安[2] 

机构地区：[1]广西师范大学药用资源化学与药物分子工程国家重点实验室培育基地,广西桂林541004 [2]分子药物教育部工程研究中心,国立华侨大学生物医学学院,福建泉州362021

出　　处：《药学学报》2013年第3期305-314,共10页Acta Pharmaceutica Sinica

基　　金：国家“重大新药创制”科技重大专项(2009ZX09103-643);国家自然科学基金资助项目(81072578);药用资源化学与药物分子工程教育部重点实验开放课题(CMEMR2012-A15)

摘　　要：如何降低免疫反应是重组腺相关病毒(rAAV)基因药物面临的重大挑战。研究表明减少载体使用剂量能够降低rAAV基因药物的免疫反应,但是减少载体使用剂量同时也会降低靶基因的表达量,甚至可能达不到治疗效果。本文重点阐述如何在减少载体使用剂量的同时,保持基因表达强度和药效。尤其侧重讨论采取给药途径优化、病毒载体改造、启动子选取在增强基因治疗效果中的应用。How to reduce immune response is an unprecedented challenge for rAAV gene medicine. Recent studies suggested that lowering dosage of the vector used could reduce immune response caused by rAAV gene medicine. Nevertheless, it would also decrease the transgene expression, leading to failure of gene treatment. It is therefore important to take appropriate steps to maintain high gene expression level and pharmacodynamic, while the dosage of rAAV used is reduced. Here, steps to enhancing gene therapy, such as optimization of the administration, reconstruction of the viral vector and selection of the promoter, are discussed in order to achieve maximum outcome.

关 键 词：免疫反应 重组腺相关病毒基因药物 载体使用量 给药途径优化 病毒载体改造 

分 类 号：R943[医药卫生—药剂学]