Tailoring recombinant protein quality by rational media design |
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| Authors: | David Brühlmann Martin Jordan Jürgen Hemberger Markus Sauer Matthieu Stettler Hervé Broly |
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| Affiliation: | 1. Merck Serono SA, Corsier‐sur‐Vevey, Biotech Process Sciences, Zone Industrielle B, Fenil‐sur‐Corsier, Switzerland;2. Dept. of Biotechnology and Biophysics, Julius‐Maximilians‐Universit?t Würzburg, Biozentrum, Würzburg, Germany;3. Inst. for Biochemical Engineering and Analytics, University of Applied Sciences Giessen, Wiesenstrasse 14, DE‐35390 Giessen, Germany |
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| Abstract: | 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, low‐molecular‐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. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:615–629, 2015 |
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| Keywords: | cell culture medium media design quality attributes therapeutic protein mammalian glycosylation |
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