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Systems Analysis in Mammalian Cell B...
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University of Minnesota.
Systems Analysis in Mammalian Cell Biomanufacturing - Linking Energy Metabolism and Glycosylation.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
Systems Analysis in Mammalian Cell Biomanufacturing - Linking Energy Metabolism and Glycosylation./
作者:
Le, Tung Sy.
面頁冊數:
1 online resource (173 pages)
附註:
Source: Dissertation Abstracts International, Volume: 79-12(E), Section: B.
Contained By:
Dissertation Abstracts International79-12B(E).
標題:
Chemical engineering. -
電子資源:
click for full text (PQDT)
ISBN:
9780438167629
Systems Analysis in Mammalian Cell Biomanufacturing - Linking Energy Metabolism and Glycosylation.
Le, Tung Sy.
Systems Analysis in Mammalian Cell Biomanufacturing - Linking Energy Metabolism and Glycosylation.
- 1 online resource (173 pages)
Source: Dissertation Abstracts International, Volume: 79-12(E), Section: B.
Thesis (Ph.D.)--University of Minnesota, 2018.
Includes bibliographical references
Mammalian cells have been the major workhorse to produce therapeutic proteins owing to their capability to perform complex post-translation modifications that are essential to the pharmacological activities of these proteins. The performance of mammalian cell culture is greatly affected by cell metabolism, while the robustness of glycosylation patterns of the product proteins still needs improvement. A meta-analysis of cell culture bioprocess data revealed a correlation between lactate metabolism, productivity, and glycosylation patterns. In this study, we develop an integrated platform for generation and visualization of the O-glycosylation network. The platform was used to explore the heterogeneity of O-glycans produced in mammalian cells. In addition, we use a kinetic model of energy metabolism to explain the mechanism behind the increase in lactate production during the late stage of fed-batch cultures. Such a metabolic behavior of lactate can have negative impacts on the culture productivity and potentially, product quality because it occurs during the main production phase. Insights from this study can be helpful in contriving strategies for more robust control of cell metabolism and obtaining consistent glycan patterns of biologics.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9780438167629Subjects--Topical Terms:
555952
Chemical engineering.
Index Terms--Genre/Form:
554714
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Systems Analysis in Mammalian Cell Biomanufacturing - Linking Energy Metabolism and Glycosylation.
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Mammalian cells have been the major workhorse to produce therapeutic proteins owing to their capability to perform complex post-translation modifications that are essential to the pharmacological activities of these proteins. The performance of mammalian cell culture is greatly affected by cell metabolism, while the robustness of glycosylation patterns of the product proteins still needs improvement. A meta-analysis of cell culture bioprocess data revealed a correlation between lactate metabolism, productivity, and glycosylation patterns. In this study, we develop an integrated platform for generation and visualization of the O-glycosylation network. The platform was used to explore the heterogeneity of O-glycans produced in mammalian cells. In addition, we use a kinetic model of energy metabolism to explain the mechanism behind the increase in lactate production during the late stage of fed-batch cultures. Such a metabolic behavior of lactate can have negative impacts on the culture productivity and potentially, product quality because it occurs during the main production phase. Insights from this study can be helpful in contriving strategies for more robust control of cell metabolism and obtaining consistent glycan patterns of biologics.
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