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Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation

In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs) must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation,...

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Autores principales: Radhakrishnan, Devesh, Robinson, Anne S., Ogunnaike, Babatunde A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698858/
https://www.ncbi.nlm.nih.gov/pubmed/31544854
http://dx.doi.org/10.3390/antib7010001
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author Radhakrishnan, Devesh
Robinson, Anne S.
Ogunnaike, Babatunde A.
author_facet Radhakrishnan, Devesh
Robinson, Anne S.
Ogunnaike, Babatunde A.
author_sort Radhakrishnan, Devesh
collection PubMed
description In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs) must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control strategies. Now, the cell culture media supplement, MnCl(2), is known to alter the glycosylation profile in mAbs generally, but its effect, particularly when introduced at different stages during cell growth, has yet to be investigated and quantified. In this study, we evaluate the effect of time-dependent addition of MnCl(2) on the glycan profile quantitatively, using factorial design experiments. Our results show that MnCl(2) addition during the lag and exponential phases affects the glycan profile significantly more than stationary phase supplementation does. Also, using a novel computational technique, we identify various combinations of glycan species that are affected by this dynamic media supplementation scheme, and quantify the effects mathematically. Our experiments demonstrate the importance of taking into consideration the time of addition of these trace supplements, not just their concentrations, and our computational analysis provides insight into what supplements to add, when, and how much, in order to induce desired changes.
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spelling pubmed-66988582019-09-05 Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation Radhakrishnan, Devesh Robinson, Anne S. Ogunnaike, Babatunde A. Antibodies (Basel) Article In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs) must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control strategies. Now, the cell culture media supplement, MnCl(2), is known to alter the glycosylation profile in mAbs generally, but its effect, particularly when introduced at different stages during cell growth, has yet to be investigated and quantified. In this study, we evaluate the effect of time-dependent addition of MnCl(2) on the glycan profile quantitatively, using factorial design experiments. Our results show that MnCl(2) addition during the lag and exponential phases affects the glycan profile significantly more than stationary phase supplementation does. Also, using a novel computational technique, we identify various combinations of glycan species that are affected by this dynamic media supplementation scheme, and quantify the effects mathematically. Our experiments demonstrate the importance of taking into consideration the time of addition of these trace supplements, not just their concentrations, and our computational analysis provides insight into what supplements to add, when, and how much, in order to induce desired changes. MDPI 2017-12-21 /pmc/articles/PMC6698858/ /pubmed/31544854 http://dx.doi.org/10.3390/antib7010001 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Radhakrishnan, Devesh
Robinson, Anne S.
Ogunnaike, Babatunde A.
Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
title Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
title_full Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
title_fullStr Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
title_full_unstemmed Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
title_short Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
title_sort controlling the glycosylation profile in mabs using time-dependent media supplementation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698858/
https://www.ncbi.nlm.nih.gov/pubmed/31544854
http://dx.doi.org/10.3390/antib7010001
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