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用于生产人源化重组药物蛋白的植物表达系统糖基工程的主要策略

Main Strategies of Plant Expression System Glycoengineering for Producing Humanized Recombinant Pharmaceutical Proteins.

作者信息

Rozov S M, Permyakova N V, Deineko E V

机构信息

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.

出版信息

Biochemistry (Mosc). 2018 Mar;83(3):215-232. doi: 10.1134/S0006297918030033.

Abstract

Most the pharmaceutical proteins are derived not from their natural sources, rather their recombinant analogs are synthesized in various expression systems. Plant expression systems, unlike mammalian cell cultures, combine simplicity and low cost of procaryotic systems and the ability for posttranslational modifications inherent in eucaryotes. More than 50% of all human proteins and more than 40% of the currently used pharmaceutical proteins are glycosylated, that is, they are glycoproteins, and their biological activity, pharmacodynamics, and immunogenicity depend on the correct glycosylation pattern. This review examines in detail the similarities and differences between N- and O-glycosylation in plant and mammalian cells, as well as the effect of plant glycans on the activity, pharmacokinetics, immunity, and intensity of biosynthesis of pharmaceutical proteins. The main current strategies of glycoengineering of plant expression systems aimed at obtaining fully humanized proteins for pharmaceutical application are summarized.

摘要

大多数药用蛋白质并非来源于其天然来源,而是其重组类似物在各种表达系统中合成。与哺乳动物细胞培养不同,植物表达系统兼具原核系统的简单性和低成本以及真核生物固有的翻译后修饰能力。超过50%的人类蛋白质和超过40%目前使用的药用蛋白质是糖基化的,即它们是糖蛋白,其生物活性、药效学和免疫原性取决于正确的糖基化模式。本文详细研究了植物和哺乳动物细胞中N-糖基化和O-糖基化之间的异同,以及植物聚糖对药用蛋白质的活性、药代动力学、免疫性和生物合成强度的影响。总结了目前植物表达系统糖基工程的主要策略,旨在获得用于药物应用的完全人源化蛋白质。

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