生物技术通报 ›› 2015, Vol. 31 ›› Issue (9): 49-59.doi: 10.13560/j.cnki.biotech.bull.1985.2015.09.007

• 综述与专论 • 上一篇    下一篇

提高重组型腺相关病毒转导效率的研究现状

殷子斐1, 王丽娜1, 王园1, 凌晨2   

  1. (1. 中国人民解放军第二军医大学,上海 200433;2.佛罗里达大学,美国佛罗里达州 32610)
  • 收稿日期:2014-11-04 出版日期:2015-09-15 发布日期:2015-09-16
  • 作者简介:殷子斐,女,博士研究生,研究方向:中医药与基因治疗的联合应用;E-mail:yinzifei870730smmu@163.com
  • 基金资助:
    国家自然科学基金项目(81303112)

Research Advances on Increasing the Transduction Efficiency of Recombinant Adeno-associated Viral Vectors

Yin Zifei1, Wang Li’na1, Wang Yuan1, Ling Chen2   

  1. (1. Second Military Medical University,People's Liberation Army,Shanghai 200433;2. University of Florida,Florida 32610)
  • Received:2014-11-04 Published:2015-09-15 Online:2015-09-16

摘要: 重组型腺相关病毒(recombinant adeno-associated virus,rAAV)载体是目前基因治疗研究中常用的、非常有前景的载体之一。欧洲第一个批准上市的基因治疗药物正是基于rAAV。然而,rAAV的转导效率相对有限,导致其治疗成本过高;且过高剂量的rAAV可以激发人体的免疫反应,降低其疗效。因此,如何提高rAAV的转导效率一直是基因治疗领域研究的热点之一。目前常用的提高rAAV转导效率的方法有:使用组织特异性强的血清型/变体、应用蛋白酶体抑制剂、突变衣壳蛋白表面裸露氨基酸、增加单链DNA的第二链合成、构建自身互补型双链载体等。就这些方法各自的原理、应用现状及优劣势进行系统地综述。

关键词: 重组腺相关病毒载体, 基因治疗, 转导效率

Abstract: The recombinant adeno-associated virus(rAAV)vector has emerged as one of the promising and commonly-used vectors in gene therapy research. The first gene therapy drug in clinic approved in Europe is based on rAAV. Due to the relatively limited transduction efficiency, the cost of the rAAV-mediated treatment is expensive. Additionally, high dose of rAAV may trigger host immune response, resulting in the curative effect reduced. Therefore, how to enhance the transduction efficiency of rAAV has been a hot issue in gene therapy. Hitherto there are five common methods to achieve this goal:selecting tissue-specific tropism serotypes and variants, using proteasome inhibitors, mutating capsid surface-exposed amino-acids, increasing second-strand DNA synthesis, and producing self-complementary vectors. In this paper we systemically review the above methods from the aspects of principle, status of application, advantages and disadvantages.

Key words: recombinant adeno-associated virus vector, gene therapy, transduction efficiency