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Valeric acid induces cell cycle arrest at G1 phase in CHO cell cultures and improves recombinant antibody productivity
Authors:Jin Hyoung Park  Soo Min Noh  Ju Rang Woo  Jong Won Kim  Gyun Min Lee
Institution:1. Department of Biological Sciences, KAIST, Daejeon, Republic of Korea;2. New Drug Development Center, Cheongju, Republic of Korea
Abstract: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 (μ), but increased culture longevity and specific mAb productivity (qmAb) in a dose‐dependent manner. The beneficial effect of valeric acid on culture longevity and qmAb outweighed its detrimental effect on μ, 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.
Keywords:Cell cycle  Chinese hamster ovary cell  Galactosylation  Specific productivity  Valeric acid
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