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Processes 2018, 6(10), 176; https://doi.org/10.3390/pr6100176

Glycosylation Flux Analysis of Immunoglobulin G in Chinese Hamster Ovary Perfusion Cell Culture

1
Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland
2
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
3
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 30 May 2018 / Revised: 12 September 2018 / Accepted: 18 September 2018 / Published: 1 October 2018
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Abstract

The terminal sugar molecules of the N-linked glycan attached to the fragment crystalizable (Fc) region is a critical quality attribute of therapeutic monoclonal antibodies (mAbs) such as immunoglobulin G (IgG). There exists naturally-occurring heterogeneity in the N-linked glycan structure of mAbs, and such heterogeneity has a significant influence on the clinical safety and efficacy of mAb drugs. We previously proposed a constraint-based modeling method called glycosylation flux analysis (GFA) to characterize the rates (fluxes) of intracellular glycosylation reactions. One contribution of this work is a significant improvement in the computational efficiency of the GFA, which is beneficial for analyzing large datasets. Another contribution of our study is the analysis of IgG glycosylation in continuous perfusion Chinese Hamster Ovary (CHO) cell cultures. The GFA of the perfusion cell culture data indicated that the dynamical changes of IgG glycan heterogeneity are mostly attributed to alterations in the galactosylation flux activity. By using a random forest regression analysis of the IgG galactosylation flux activity, we were further able to link the dynamics of galactosylation with two process parameters: cell-specific productivity of IgG and extracellular ammonia concentration. The characteristics of IgG galactosylation dynamics agree well with what we previously reported for fed-batch cultivations of the same CHO cell strain. View Full-Text
Keywords: N-linked glycosylation; perfusion cell culture; CHO cells; constraint-based modeling; monoclonal antibody N-linked glycosylation; perfusion cell culture; CHO cells; constraint-based modeling; monoclonal antibody
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Hutter, S.; Wolf, M.; Papili Gao, N.; Lepori, D.; Schweigler, T.; Morbidelli, M.; Gunawan, R. Glycosylation Flux Analysis of Immunoglobulin G in Chinese Hamster Ovary Perfusion Cell Culture. Processes 2018, 6, 176.

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