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作为双功能展示支架的噬菌体:在纳米尺度上设计瑞士军刀

Bacteriophages as scaffolds for bipartite display: designing swiss army knives on a nanoscale.

作者信息

Molek Peter, Bratkovič Tomaž

机构信息

University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Biology, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.

出版信息

Bioconjug Chem. 2015 Mar 18;26(3):367-78. doi: 10.1021/acs.bioconjchem.5b00034. Epub 2015 Feb 13.

DOI:10.1021/acs.bioconjchem.5b00034
PMID:25654261
Abstract

Bacteriophages have been exploited as cloning vectors and display vehicles for decades owing to their genetic and structural simplicity. In bipartite display setting, phage takes on the role of a handle to which two modules are attached, each endowing it with specific functionality, much like the Swiss army knife. This concept offers unprecedented potential for phage applications in nanobiotechnology. Here, we compare common phage display platforms and discuss approaches to simultaneously append two or more different (poly)peptides or synthetic compounds to phage coat using genetic fusions, chemical or enzymatic conjugations, and in vitro noncovalent decoration techniques. We also review current reports on design of phage frameworks to link multiple effectors, and their use in diverse scientific disciplines. Bipartite phage display had left its mark in development of biosensors, vaccines, and targeted delivery vehicles. Furthermore, multifunctionalized phages have been utilized to template assembly of inorganic materials and protein complexes, showing promise as scaffolds in material sciences and structural biology, respectively.

摘要

由于噬菌体在遗传和结构上的简单性,它们作为克隆载体和展示载体已被应用了数十年。在二分体展示体系中,噬菌体充当一个把手的角色,两个模块附着其上,每个模块赋予其特定功能,这很像瑞士军刀。这一概念为噬菌体在纳米生物技术中的应用提供了前所未有的潜力。在这里,我们比较了常见的噬菌体展示平台,并讨论了使用基因融合、化学或酶促偶联以及体外非共价修饰技术将两种或更多种不同的(多)肽或合成化合物同时连接到噬菌体衣壳上的方法。我们还综述了当前关于连接多个效应器的噬菌体框架设计及其在不同科学领域应用的报道。二分体噬菌体展示在生物传感器、疫苗和靶向递送载体的开发中留下了印记。此外,多功能化噬菌体已被用于无机材料和蛋白质复合物的模板组装,分别在材料科学和结构生物学中有望作为支架发挥作用。

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