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Chinese Hamster Ovary Cell Line Instability: Causes, Mitigation, and Prediction

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Abstract

Cell line instability is a common problem in biopharmaceutical manufacturing using Chinese hamster ovary (CHO) cells. Cell line instability, which refers to unintended and unpredicted genetic, epigenetic, and phenotypic changes over time, can increase production costs and threaten sales approval by reducing product quantity and quality. While a stability test is conducted to screen cell lines with stable transgene expression, this process requires several months, delaying the entire drug development timeline. To accelerate timeline for drug development, understanding, mitigation, and prediction of cell line instability are critical. In this review, we update recent research progresses regarding instability-inducing biological mechanisms and alleviating the intrinsic instability of CHO cells. We also discuss studies that contribute to predicting irregular phenotypic changes in recombinant protein-producing CHO cell lines, based on omics-based studies. These prediction strategies will contribute to complementing current instability alleviating strategies, thereby saving labor, cost, and time for the cell line development process as well as providing a comprehensive understanding of CHO cell biology.

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Acknowledgements

This work was supported by Inha University Research Grant.

Author information

Author notes

  1. Yun Joo and Hagyeong Kim contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Engineering, Inha University, Incheon, 22212, Korea

    Yun Joo, Hagyeong Kim & Jong Youn Baik

  2. Department of Biological Sciences and Bioengineering, Inha University, Incheon, 22212, Korea

    Yun Joo, Hagyeong Kim & Jong Youn Baik

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  1. Yun Joo
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  2. Hagyeong Kim
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  3. Jong Youn Baik
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Correspondence to Jong Youn Baik.

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Joo, Y., Kim, H. & Baik, J.Y. Chinese Hamster Ovary Cell Line Instability: Causes, Mitigation, and Prediction. Biotechnol Bioproc E 28, 750–760 (2023). https://doi.org/10.1007/s12257-023-0120-6

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