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  • 标题:Compartmental Glycosylation Flux Analysis
  • 本地全文:下载
  • 作者:Shilpi Aggarwal ; Xin Qi ; Sriram Neelamegham
  • 期刊名称:IFAC PapersOnLine
  • 印刷版ISSN:2405-8963
  • 出版年度:2021
  • 卷号:54
  • 期号:3
  • 页码:287-293
  • DOI:10.1016/j.ifacol.2021.08.256
  • 语种:English
  • 出版社:Elsevier
  • 摘要:AbstractN-linked glycosylation is a critical quality attribute of therapeutic monoclonal antibodies (mAbs) – an important class of biologics. In this work, we developed compartmental Glycosylation Flux Analysis (cGFA) to enable a more accurate representation of the cell’s Golgi apparatus (GA), where protein glycosylation takes place, in the analysis of intracellular fluxes of glycosylation reactions. The application of one-compartment and two-compartment cGFA to a Chinese hamster ovary cell culture production of immunoglobulin G demonstrated the insufficiency of modeling the GA as one well-mixed compartment. The two-compartment cGFA was able to, not only fit the data significantly better than the one-compartment cGFA, but also accurately predict the localization of enzyme in the GA cisternae. Information on glycosylation alterations during cell cultivation, as provided by the cGFA, may lead to a better understanding of how different cell culture parameters control the N-linked glycosylation which would enable a more precise glycoengineering of therapeutic mAbs.
  • 关键词:Keywordsglycosylationflux analysismonoclonal antibodiesChinese hamster ovary
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