Enhanced Production of Monomeric Interferon-β by CHO Cells through the Control of Culture Conditions
Abstract
The enhancement of recombinant protein expression of a transfected cell line is essential for the development of an efficient large-scale bioprocess. The effect of various media additives and temperature conditions were studied in an attempt to optimize protein production, stability, and protein glycosylation from a Chinese hamster ovary (CHO) cell line producing human beta-interferon (Hu-beta-IFN). We observed a decrease in the ELISA response of the glycoprotein in the later stages of batch cultures, which was attributed to molecular aggregation. Cells were subjected to various concentrations of glycerol, dimethyl sulfoxide (DMSO), and sodium butyrate (NaBu) in a variety of culture systems and conditions. The addition of both NaBu and DMSO resulted in higher specific productivities but reduced growth rates that resulted in a net reduction of interferon produced. Glycerol appeared to stabilize the secreted beta-IFN, resulting in reduced aggregation, despite a decrease in cell growth rate. Glycosylation analysis of isolated beta-IFN showed a time-dependent decrease in sialylation in batch culture that was ameliorated by the presence of glycerol. Low-temperature conditions (30 degrees C) had the greatest effect on productivity with a significant increase in beta-IFN titer as well as a reduction in the degree of molecular aggregation.
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Optimization of the addition timing and concentration of histone deacetylase inhibitors has shown to be important to attenuate their undesired effects.
“To attenuate these effects, optimization of the addition timing and concentration has shown to be important (Rodriguez et al., 2005).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Rodriguez et al., 2005
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Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
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Ha, T. K., Hansen, A. H., Kol, S., Kildegaard, H. F., & Lee, G. M. (2018) · Biotechnology Journal · doi:10.1002/biot.201700425 · Cited by 40 · see citing works
Ha, T. K., Hansen, A. H., Kildegaard, H. F., & Lee, G. M. (2019) · Biotechnology Journal · doi:10.1002/biot.201900130 · Cited by 30 · see citing works
- Authors
- Rodriguez, J., Spearman, M., Huzel, N., & Butler, M.
- Affiliations
- University of Manitoba (CA)
- Corresponding author
- Butler, M.
- ORCID
- Butler, M.
- Venue
- Biotechnology Progress
- Publisher
- Wiley
- Published
- 2008-09-05
- Volume
- 21
- Issue
- 1
- Pages
- 22-30
- ISSN
- 1520-6033 (ISSN-L)
- 8756-7938
- OpenAlex
- W2010385141
- Cited by
- 145
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 13 · 2017: 7 · 2016: 5 · 2015: 8 · 2014: 12 · 2013: 11 · 2012: 4
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology Progress (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Transgenic Plants and Applications
- Keywords
- interferon-beta, recombinant protein expression, CHO cells, protein stability, glycosylation, sialylation, glycerol, dimethyl sulfoxide, sodium butyrate, low-temperature cultivation, batch culture, culture condition optimization, specific productivity
- MeSH terms
- Animals, Butyrates, Cells, Cultured, Culture Media, Dimethyl Sulfoxide, Glycerol, Glycosylation, Cricetinae, Humans, Temperature, Time Factors, Transfection, CHO Cells, Interferon-beta, Culture Techniques, Cell Proliferation
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