Tailoring Recombinant Protein Quality by Rational Media Design
Tailoring Recombinant Protein Quality by Rational Media Design
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DOI：
10.1002/btpr.2089
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发表时间：
2015-05-01
影响因子：
2.9
通讯作者：
Broly, Herve
中科院分区：
文献类型：
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作者：
Bruehlmann, David;Jordan, Martin;Broly, Herve
重组蛋白的临床疗效和安全性与其结构特征密切相关。主要质量属性包括糖基化、电荷变体（氧化、脱酰胺和C-和N-末端修饰）、聚集体、低分子量物质（LMW）和蛋白质骨架中氨基酸的错误掺入。由于培养基在哺乳动物细胞培养中的重要作用，细胞培养基设计具有调节这些质量属性的巨大潜力。本综述的目的是提供一个概述的方式都经典的细胞培养基成分和新的补充剂影响的质量属性的重组治疗蛋白在哺乳动物宿主中表达，允许合理和高通量优化哺乳动物细胞培养基。介绍了一系列寡糖加工的特异性和/或强效抑制剂和活化剂以及影响多种质量属性的组分。在这一领域的广泛研究工作表明，通过培养基设计进行质量工程的可行性，可以显着调节蛋白质功能。(C)2015年美国化学工程师学会
Clinical efficacy and safety of recombinant proteins are closely associated with their structural characteristics. The major quality attributes comprise glycosylation, charge variants (oxidation, deamidation, and C- & N-terminal modifications), aggregates, lowmolecular- weight species (LMW), and misincorporation of amino acids in the protein backbone. Cell culture media design has a great potential to modulate these quality attributes due to the vital role of medium in mammalian cell culture. The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high-throughput optimization of mammalian cell culture media. A selection of specific and/or potent inhibitors and activators of oligosaccharide processing as well as components affecting multiple quality attributes are presented. Extensive research efforts in this field show the feasibility of quality engineering through media design, allowing to significantly modulate the protein function. (C) 2015 American Institute of Chemical Engineers