Bacteriophage Capsid Modification by Genetic and Chemical Methods.

Bacteriophage Capsid Modification by Genetic and Chemical Methods.
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DOI:
10.1021/acs.bioconjchem.1c00018
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发表时间:
2021-03-17
影响因子:
4.7
通讯作者:
Nugen SR
Nugen SR
中科院分区:
化学2区
文献类型:
--
作者:
Carmody CM;Goddard JM;Nugen SR

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噬菌体是一种病毒,它在自然界中无处不在,对宿主细菌具有显著的特异性,使可调生物技术在农业和公共卫生领域的应用令人印象深刻。噬菌体衣壳容纳和保护它们的核酸,已经用一系列功能(如荧光团、纳米粒子、抗原、药物)进行了修饰,以适应它们的最终应用。天然存在于噬菌体衣壳上的官能团可用于静电吸附或生物偶联,但它们的非永久性和较差的特异性会导致覆盖范围和功能的不一致。为了克服这些限制,研究人员已经探索了遗传和化学修饰,以使噬菌体衣壳和它们的靶偶联物之间建立强大的、特定的结合。遗传修饰方法包括将替代氨基酸、肽或蛋白质序列的基因引入噬菌体基因组或宿主质粒上的衣壳基因中,以促进重组噬菌体的产生。化学修饰方法依赖于在适当的溶液pH和盐条件下,将衣壳上的官能团与活化的偶联物反应。本文综述了遗传和化学噬菌体衣壳修饰方法的最新进展,确定了这些方法的主要优点和缺点,并讨论了在生物传感器、疫苗、疗法和纳米载体的开发中推动噬菌体技术所需的研究领域。
Bacteriophages are viruses whose ubiquity in nature and remarkable specificity to their host bacteria enable an impressive and growing field of tunable biotechnologies in agriculture and public health. Bacteriophage capsids, which house and protect their nucleic acids, have been modified with a range of functionalities (e.g. fluorophores, nanoparticles, antigens, drugs) to suit their final application. Functional groups naturally present on bacteriophage capsids can be used for electrostatic adsorption or bioconjugation but their impermanence and poor specificity can lead to inconsistencies in coverage and function. To overcome these limitations, researchers have explored both genetic and chemical modifications to enable strong, specific bonds between phage capsids and their target conjugates. Genetic modification methods involve introducing genes for alternative amino acids, peptides, or protein sequences into either the bacteriophage genomes or capsid genes on host plasmids to facilitate recombinant phage generation. Chemical modification methods rely on reacting functional groups present on the capsid with activated conjugates under the appropriate solution pH and salt conditions. This review surveys the current state-of-the-art in both genetic and chemical bacteriophage capsid modification methodologies, identifies major strengths and weaknesses of methods, and discusses areas of research needed to propel bacteriophage technology in development of biosensors, vaccines, therapeutics, and nanocarriers.
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