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植物中生物治疗蛋白的糖基工程。

Glyco-engineering of biotherapeutic proteins in plants.

作者信息

Ko Kisung, Ahn Mi-Hyun, Song Mira, Choo Young-Kug, Kim Hyun Soon, Ko Kinarm, Joung Hyouk

机构信息

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 570-749, Korea.

出版信息

Mol Cells. 2008 Jun 30;25(4):494-503. Epub 2008 Apr 23.

Abstract

Many therapeutic glycoproteins have been successfully generated in plants. Plants have advantages regarding practical and economic concerns, and safety of protein production over other existing systems. However, plants are not ideal expression systems for the production of biopharmaceutical proteins, due to the fact that they are incapable of the authentic human N-glycosylation process. The majority of therapeutic proteins are glycoproteins which harbor N-glycans, which are often essential for their stability, folding, and biological activity. Thus, several glyco-engineering strategies have emerged for the tailor-making of N-glycosylation in plants, including glycoprotein subcellular targeting, the inhibition of plant specific glycosyltranferases, or the addition of human specific glycosyltransferases. This article focuses on plant N-glycosylation structure, glycosylation variation in plant cell, plant expression system of glycoproteins, and impact of glycosylation on immunological function. Furthermore, plant glyco-engineering techniques currently being developed to overcome the limitations of plant expression systems in the production of therapeutic glycoproteins will be discussed in this review.

摘要

许多治疗性糖蛋白已在植物中成功产生。与其他现有系统相比,植物在实际和经济考量以及蛋白质生产安全性方面具有优势。然而,植物并非生产生物制药蛋白质的理想表达系统,因为它们无法进行真正的人类N-糖基化过程。大多数治疗性蛋白质是带有N-聚糖的糖蛋白,这些N-聚糖通常对其稳定性、折叠和生物活性至关重要。因此,出现了几种用于在植物中定制N-糖基化的糖工程策略,包括糖蛋白亚细胞靶向、抑制植物特异性糖基转移酶或添加人类特异性糖基转移酶。本文重点关注植物N-糖基化结构、植物细胞中的糖基化变异、糖蛋白的植物表达系统以及糖基化对免疫功能的影响。此外,本综述将讨论目前正在开发的植物糖工程技术,以克服植物表达系统在生产治疗性糖蛋白方面的局限性。

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