腺相关病毒的衣壳装配和DNA衣壳化机制.PDFVIP

生 物 工 程 学 报 Chin J Biotech 2011, April 25; 27(4): 531−538 Chinese Journal of Biotechnology ISSN 1000-3061 cjb@ ©2011 CJB, All rights reserved. 综 述 腺相关病毒的衣壳装配和DNA 衣壳化机制 1,2 1,2 1,2 1,2 1,2 王启钊 ，吕颖慧 ，李招发 ，刁勇 ，许瑞安 1 华侨大学分子药物学研究所，泉州 362021 2 分子药物教育部工程研究中心，泉州 362021 摘 要: 重组腺相关病毒载体 (rAAV) 是基因治疗临床应用载体的选择之一。在简述野生型AAV 基因组结构和复制 机制的基础上，阐述了AAV 包装过程中两个主要事件：衣壳蛋白的装配和基因组DNA 的衣壳化。虽然对AAV 的包装 机制总体上已有一定的认识，但其详细的分子机制、构效关系仍需完善和充实。AAV 病毒本身相关机制的深入研究有 助于改善rAAV 载体的制备技术，促进rAAV 基因药物研发。 关键词: 腺相关病毒，装配，衣壳化，基因治疗 Capsid assembly and DNA encapsidation of adeno-associated virus Qizhao Wang1,2, Yinghui Lü1,2, Zhaofa Li1,2, Yong Diao1,2, and Rui’an Xu1,2 1 Institute of Molecular Medicine , Huaqiao University, Quanzhou 362021, China 2 Molecular Medicine Engineering Research Center, Ministry of Education, Quanzhou 362021, China Abstract: Recombinant adeno-associated viral vectors (rAAV) have been widely used as gene therapy vectors in clinical trials. Here, we reviewed the genomic structures and replication mechanisms of wt-AAV. Then, the assembly of capsid and the encapsidation of genomic DNA, two major events during AAV pakaging, was discussed in detail. Although the overall pattern of virus assembly and encapsidation is known, the molecular mechanisms and the structure-function relationship involved in these processes are not well understood. Further elucidatation of these processes may improve the production technology of rAAV and develop gene drug based on rAAV. Keywords: adeno-assoicated virus, assembly, encapsidation, gene therapy Recei