摘要
重组型腺相关病毒(recombinant adeno-associated virus,r AAV)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r AAV。然而,r AAV的转导效率相对有限,导致其治疗成本过高;且过高剂量的r AAV可以激发人体的免疫反应,降低其疗效。因此,如何提高r AAV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r AAV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。
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.
出处
《生物技术通报》
CAS
CSCD
北大核心
2015年第9期49-59,共11页
Biotechnology Bulletin
基金
国家自然科学基金项目(81303112)
关键词
重组腺相关病毒载体
基因治疗
转导效率
recombinant adeno-associated virus vector
gene therapy
transduction efficiency
