摘要
重组腺相关病毒(rAAV)载体是一种具有高靶向性和良好安全性的病毒载体,在基因治疗中得到了较为广泛的应用。目前全球范围内已有70余项以rAAV为基因药物的临床研究已经完成或正在进行中。与野生型AAV(wtAAV)定点整合不同,不表达Rep蛋白的rAAV载体与宿主染色体发生的是随机整合,而这给临床应用带来了可能的潜在的安全隐患。该文在综述wtAAV和rAAV整合机理的基础上对rAAV的因随机整合而可能导致的致癌性及其他后果进行探讨,并总结了相应应对策略,特别是目前利用Rep蛋白所开展的定点整合研究。
Recombinant adeno-associated viral vectors （rAAV） have been extensively applied in gene therapy for its high safety and specific targeting activity. More than 70 clinical trials have demonstrated the efficacy of rAAV based gene drugs. Unlike wild type AAV （wtAAV）, which is able to integrate into a specific locus of human chromosome 19, rAAV randomly integrates in chromosomes for lack of rep expression. The random integration of rAAV may induce a potential danger in clinical. This review presents the progress of the mechanisms for wtAAV and rAAV, and discuss the potential consequences （including carcinogenicity） that caused by the random integration of rAAV. Moreover, the strategies, especially using Rep protein to improve the site-specific integration is also reviewed.
出处
《生命科学》
CSCD
北大核心
2010年第5期459-465,共7页
Chinese Bulletin of Life Sciences
基金
国家“863”项目(2008AA02Z135)
福建省发改委项目,2008年第三批[26]
关键词
腺相关病毒
定点整合
随机整合
REP蛋白
安全性
adeno-associated virus
site-specific integration
random integration
Rep protein
safety
