Journal
BIOTECHNOLOGY JOURNAL
Volume 11, Issue 4, Pages 487-496Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.201500327
Keywords
Cell cycle; Chinese hamster ovary cell; Galactosylation; Specific productivity; Valeric acid
Funding
- intelligent synthetic biology center of global frontier project - MEST [2011-0031962]
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIP) [2014069603]
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To find a more effective chemical reagent for improved monoclonal antibody (mAb) production, eight chemical reagents (curcumin, quercein, DL-sulforaphane, thymidine, valeric acid, phenyl butyrate, valproic acid, and lithium chloride) known to induce cell cycle arrest were examined individually as chemical additives to recombinant CHO (rCHO) cell cultures producing mAb. Among these chemical additives, valeric acid showed the best production performance. Valeric acid decreased specific growth rate (), but increased culture longevity and specific mAb productivity (q(mAb)) in a dose-dependent manner. The beneficial effect of valeric acid on culture longevity and q(mAb) outweighed its detrimental effect on , resulting in 2.9-fold increase in the maximum mAb concentration when 1.5 mM valeric acid was added to the cultures. Furthermore, valeric acid did not negatively affect the mAb quality attributes with regard to aggregation, charge variation, and galactosylation. Unexpectedly, galactosylation of the mAb increased by the 1.5 mM valeric acid addition. Taken together, the results obtained here demonstrate that valeric acid is an effective chemical reagent to increase mAb production in rCHO cells.
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