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Dynamic model for CHO cell engineering

Paper ID Volume ID Publish Year Pages File Format Full-Text
23668 43461 2012 10 PDF Available
Title
Dynamic model for CHO cell engineering
Abstract

Industrial CHO cell fed-batch processes have progressed significantly over the past decade, with recombinant protein titer consistently reaching the gram per liter level. Such improvements have largely resulted from separate advances in process and cell line development. Model-based selection of targets for metabolic engineering in CHO cells is confounded by the dynamic nature of the fed-batch process. In this work, we use a dynamic model of CHO cell metabolism to simultaneously identify both process and cell modifications that improve antibody production. Model simulations explored ca. 9200 combinations of process variables (shift temperature, shift day, seed density, and harvest day) and knockdowns (8 metabolic enzymes). A comprehensive examination of a simulated solution space showed that optimal gene knockdown clearly depends on the process parameters such as temperature shift day, shift temperature, and seed density. Knockdown of enzymes related to lactate production were the most beneficial; however, depending on the process conditions, modulating such enzymes yielded varying productivities, ranging from a reduction in final titer to greater than 2-fold improvement.

► Engineering of CHO cells in fed-batch culture needs to consider the process dynamics. ► Dynamic simulations explored ∼9200 combinations of process and cell modifications. ► Optimal enzyme knockdown depends on the process conditions. ► Knockdown of enzymes in glycolysis were generally the most beneficial. ► Depending on the process, such knockdowns reduced or increased the antibody titer.

Keywords
CHO cell engineering; Fed-batch; Dynamic model; Process simulation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 158, Issues 1–2, 31 March 2012, Pages 24–33
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us