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Received May 20, 2010
Accepted June 9, 2010
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This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/3.0) which permits
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Cellular engineering for the high-level production of recombinant proteins in mammalian cell systems
School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea
thpark@snu.ac.kr
Korean Journal of Chemical Engineering, July 2010, 27(4), 1042-1048(7), 10.1007/s11814-010-0278-4
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Abstract
The market for protein-drugs has steadily increased due their increased use as alternatives to traditional small molecule drugs. While some therapeutic proteins have been produced in microbial systems, mammalian cell systems such as Chinese hamster ovary (CHO) cells are widely used as the host cell system. To increase the efficiency of producing therapeutic proteins, many researchers have attempted to solve the critical problems that occur in mammalian cell systems. As a result, several serum-free media and advanced culture methods have been developed, and protein productivity has increased considerably through the development of efficient selection methods. However, the prevalence of apoptosis during mammalian cell culture still remains a significant problem. Based on the understanding of apoptotic mechanisms and related proteins, anti-apoptotic engineering has steadily progressed. In this study, we review the strategies that have been developed for high-level production of recombinant proteins in the CHO cell system via a selection of clones, target-gene amplification, optimization of culture systems and an inhibition of apoptosis through genetic modification.
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References
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Liu X, Kim CN, Yang J, Jemmerson R, Wang X, Cell., 86, 147 (1996)
Ashkenazi A, Nat. Rev. Cancer., 2, 420 (2002)
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Adam JM, Cory S, Curr. Opin. Cell Biol., 14, 715 (2002)
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Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM, Nature, 379(6565), 554 (1996)
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Wang Z, Park JH, Park HH, Tan W, Park TH, Process Biochem., in press, doi:10.1016/j.procbio.2010.03.029 (2010)
