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迈向增强治疗性糖蛋白生物生产:对PI3K/AKT/mTOR信号通路的干预

Towards Enhancing Therapeutic Glycoprotein Bioproduction: Interventions in the PI3K/AKT/mTOR Pathway.

作者信息

Mahameed Mohamed, Sulieman Afnan, Alkam Duah, Tirosh Boaz

机构信息

Institute for Drug Research, The Hebrew University of Jerusalem.

Department of Biomedical Informatics, University of Arkansas for Medical Sciences.

出版信息

Cell Struct Funct. 2019;44(2):75-83. doi: 10.1247/csf.19013.

DOI:10.1247/csf.19013
PMID:31353334
Abstract

Recombinant glycoproteins produced in mammalian cells are clinically indispensable drugs used to treat a broad spectrum of diseases. Their bio-manufacturing process is laborious, time consuming, and expensive. Investment in expediting the process and reducing its cost is the subject of continued research. The PI3K/Akt/mTOR signaling pathway is a key regulator of diverse physiological functions such as proliferation, global protein, and lipid synthesis as well as many metabolic pathways interacting to increase secretory capabilities. In this review we detail various strategies previously employed to increase glycoprotein production yields via either genetic or pharmacological over-activation of the PI3K/Akt/mTOR pathway, and we discuss their potential and limitations.Key words: mTORC1, CRISPR, specific productivity, translation.

摘要

在哺乳动物细胞中产生的重组糖蛋白是临床上治疗多种疾病不可或缺的药物。其生物制造过程繁琐、耗时且成本高昂。加快该过程并降低成本的投资是持续研究的主题。PI3K/Akt/mTOR信号通路是多种生理功能的关键调节因子,如增殖、整体蛋白质和脂质合成以及许多相互作用以提高分泌能力的代谢途径。在本综述中,我们详细介绍了先前通过PI3K/Akt/mTOR途径的基因或药理学过度激活来提高糖蛋白产量的各种策略,并讨论了它们的潜力和局限性。关键词:mTORC1、CRISPR、比生产率、翻译

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