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Mechanistic understanding of CHO cell culture improvement by rosmarinic acid through multi-omics analysis
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  • Zhuangrong Huang,
  • Jianlin Xu,
  • Jun Tian,
  • Kathryn Aron,
  • Yueming Qian,
  • Michael Borys,
  • Zheng Jian Li,
  • Girish Pendse
Zhuangrong Huang
Bristol-Myers Squibb Co
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Jianlin Xu
Bristol-Myers Squibb Company
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Jun Tian
WuXi Biologics
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Kathryn Aron
Bristol-Myers Squibb Co
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Yueming Qian
Bristol-Myers Squibb
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Michael Borys
Bristol-Myers Squibb Company
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Zheng Jian Li
Bristol-Myers Squibb Company
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Girish Pendse
Bristol-Myers Squibb Co
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Abstract

The use of antioxidants in Chinese hamster ovary (CHO) cell cultures to improve monoclonal antibody production has been a topic of great interest. Nevertheless, the mechanisms by which antioxidant pathways are regulated in CHO cells and their effect on metabolism are not fully understood. In this work, we investigated how treatment with the antioxidant rosmarinic acid (RA) improved viable cell density and titer in CHO cell cultures, and attempted to explore the underlying mechanism(s) using transcriptomics and metabolomics. In particular, transcriptomics analysis indicated that RA treatment modified gene expression and strongly affected the MAPK and Akt signaling pathways which regulate cell survival and cell death. Moreover, we observed that these effects did not appear related to an intracellular metabolism change. In summary, this integrated ‘omics analysis has important implications for the role of the antioxidant RA in industrial cell culture processes. The current study also represents an example in the industry of how multi-omics can be applied to gain an in‐depth understanding of CHO cell biology and to identify critical pathways that can contribute to cell culture process improvement and cell line engineering.