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杆状病毒展示:一种用于基因递送和真核文库开发的多功能技术。

Baculovirus display: a multifunctional technology for gene delivery and eukaryotic library development.

作者信息

Mäkelä Anna R, Oker-Blom Christian

机构信息

Department of Biological and Environmental Science, NanoScience Center University of Jyväskylä, FIN-40014, Finland.

出版信息

Adv Virus Res. 2006;68:91-112. doi: 10.1016/S0065-3527(06)68003-2.

Abstract

For over a decade, phage display has proven to be of immense value, allowing selection of a large variety of genes with novel functions from diverse libraries. However, the folding and modification requirements of complex proteins place a severe constraint on the type of protein that can be successfully displayed using this strategy, a restriction that could be resolved by similarly engineering a eukaryotic virus for display purposes. The quite recently established eukaryotic molecular biology tool, the baculovirus display vector system (BDVS), allows combination of genotype with phenotype and thereby enables presentation of eukaryotic proteins on the viral envelope or capsid. Data have shown that the baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is a versatile tool for eukaryotic virus display. Insertion of heterologous peptides and/or proteins into the viral surface by utilizing the major envelope glycoprotein gp64, or foreign membrane-derived counterparts, allows incorporation of the sequence of interest onto the surface of infected cells and virus particles. A number of strategies are being investigated in order to further develop the display capabilities of AcMNPV and improve the complexity of a library that may be accommodated. Numerous expression vectors for various approaches of surface display have already been developed. Further improvement of both insertion and selection strategies toward development of a refined tool for use in the creation of useful eukaryotic libraries is, however, needed. Here, the status of baculovirus display with respect to alteration of virus tropism, antigen presentation, transgene expression in mammalian cells, and development of eukaryotic libraries will be reviewed.

摘要

十多年来,噬菌体展示已被证明具有巨大价值,它能够从各种文库中筛选出大量具有新功能的基因。然而,复杂蛋白质的折叠和修饰要求对使用该策略成功展示的蛋白质类型施加了严格限制,这一限制可通过类似地改造真核病毒用于展示目的来解决。最近建立的真核分子生物学工具——杆状病毒展示载体系统(BDVS),允许将基因型与表型相结合,从而使真核蛋白质能够呈现在病毒包膜或衣壳上。数据表明,杆状病毒苜蓿银纹夜蛾多核型多角体病毒(AcMNPV)是用于真核病毒展示的多功能工具。通过利用主要包膜糖蛋白gp64或源自外膜的对应物,将异源肽和/或蛋白质插入病毒表面,可使感兴趣的序列整合到受感染细胞和病毒颗粒的表面。为了进一步开发AcMNPV的展示能力并提高可容纳文库的复杂性,正在研究多种策略。已经开发了许多用于各种表面展示方法的表达载体。然而,仍需要进一步改进插入和选择策略,以开发一种用于创建有用真核文库的精细工具。在此,将综述杆状病毒展示在病毒嗜性改变、抗原呈递、哺乳动物细胞中的转基因表达以及真核文库开发方面的现状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe82/7112267/185734e1ce58/gr1.jpg

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