A metabolic network-based approach for developing feeding strategies for CHO cells to increase monoclonal antibody production

Bioprocess and Biosystems Engineering - Tập 43 - Trang 1381-1389 - 2020
Hamideh Fouladiha1, Sayed-Amir Marashi1, Fatemeh Torkashvand2, Fereidoun Mahboudi2, Nathan E. Lewis3,4,5, Behrouz Vaziri2
1Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
2Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3Department of Bioengineering, University of California, San Diego, USA
4Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego, USA
5Department of Pediatrics, University of California, San Diego, USA

Tóm tắt

Chinese hamster ovary (CHO) cells are the main workhorse in the biopharmaceutical industry for the production of recombinant proteins, such as monoclonal antibodies. To date, a variety of metabolic engineering approaches have been used to improve the productivity of CHO cells. While genetic manipulations are potentially laborious in mammalian cells, rational design of CHO cell culture medium or efficient fed-batch strategies are more popular approaches for bioprocess optimization. In this study, a genome-scale metabolic network model of CHO cells was used to design feeding strategies for CHO cells to improve monoclonal antibody (mAb) production. A number of metabolites, including threonine and arachidonate, were suggested by the model to be added into cell culture medium. The designed composition has been experimentally validated, and then optimized, using design of experiment methods. About a two-fold increase in the total mAb expression has been observed using this strategy. Our approach can be used in similar bioprocess optimization problems, to suggest new ways of increasing production in different cell factories.

Tài liệu tham khảo

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