CHO cells in biotechnology for production of recombinant proteins: current state and further potential
Abstract
Recombinant Chinese hamster ovary cells (rCHO) cells have been the most commonly used mammalian host for large-scale commercial production of therapeutic proteins. Recent advances in cell culture technology for rCHO cells have achieved significant improvement in protein production leading to titer of more than 10 g/L to meet the huge demand from market needs. This achievement is associated with progression in the establishment of high and stable producer and the optimization of culture process including media development. In this review article, we focus on current strategies and achievements in cell line development, mainly in vector engineering and cell engineering, for high and stable protein production in rCHO cells. The approaches that manipulate various DNA elements for gene targeting by site-specific integration and cis-acting elements to augment and stabilize gene expression are reviewed here. The genetic modulation strategy by "direct" cell engineering with growth-promoting and/or productivity-enhancing factors and omics-based approaches involved in transcriptomics, proteomics, and metabolomics to pursue cell engineering are also presented.
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CHO cells can achieve substantial production rate, are suitable for large-scale industrial suspension culture, and can be adapted to grow in various serum-free and chemically defined culture media.
“These cells can achieve substantial production rate, are suitable for large-scale industrial suspension culture and can be adapted to grow in various serum-free and chemically defined culture media (Kim et al., 2012;Lai et al., 2013).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
Among mammalian-based expression systems, CHO cells are by far the most commonly used cell line.
“Among the mammalian-based expression systems, CHO cells is by far, the most commonly used cell line.”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
Different gene amplification systems developed and used in CHO cells allow high titer yields and good specific productivity.
“Moreover, different gene amplification systems have been developed and used in CHO cells, which allow for high titer yields and good specific productivity (Durocher and Butler, 2009;Kim et al., 2012;Lai et al., 2013).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
CHO cells are involved in the production of over 70% of recombinant biopharmaceutical proteins, most of them monoclonal antibodies.
“It is involved in the production of over 70% of recombinant biopharmaceutical proteins, most of them being monoclonal antibodies (mAbs) (Durocher and Butler, 2009;Kim et al., 2012;Butler and Spearman, 2014).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
Because CHO cells produce recombinant glycoproteins with human-like glycans, the generated products are more likely to be compatible and bioactive within human hosts.
“Since CHO cells produce recombinant glycoproteins with human-like glycans, the generated products are to more likely be compatible and bioactive within human hosts (Kim et al., 2012;Lai et al., 2013).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
Several recombinases have been used for targeted site approaches, among which Cre/Lox and Flp/FRT were mostly utilized.
“As first generation tools, several recombinases have been used for targeted site approaches, among which the Cre/Lox and the Flp/FRT were mostly utilized (Kito et al., 2002;Huang et al., 2007;Kim et al., 2012).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
Although the effects on cell longevity are clear in anti-apoptosis studies, many conflicting results regarding enhanced productivity with anti-apoptosis engineering have been reported.
“Although the effects on cell longevity are clear in these studies, many conflicting results regarding enhanced productivity with anti-apoptosis engineering have been reported (Kim et al., 2012).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
Anti-autophagy engineering and metabolic engineering have been used in order to optimize recombinant protein production in mammalian cells.
“Among these approaches, anti-autophagy engineering and metabolic engineering have been used in order to optimize recombinant protein production in mammalian cells (for a detailed review on the topic see (Kim et al., 2012;Kim et al., 2013)).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kim et al., 2012
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- Authors
- Kim, J. Y., Kim, Y.-G., & Lee, G. M.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Corresponding author
- Lee, Gyun Min
- Venue
- Applied Microbiology and Biotechnology
- Published
- 2011-12-09
- Volume
- 93
- Issue
- 3
- Pages
- 917-930
- ISSN
- 0175-7598 (ISSN-L)
- 1432-0614
- OpenAlex
- W2027783748
- Cited by
- 801
- References
- 5
- Citations by year
- 2026: 42 · 2025: 57 · 2024: 72 · 2023: 49 · 2022: 43 · 2021: 60 · 2020: 48 · 2019: 59 · 2018: 71 · 2017: 58 · 2016: 50 · 2015: 62 · 2014: 57 · 2013: 53 · 2012: 15
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Applied Microbiology and Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- KRIBB Repository (submittedVersion)
- 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
- CHO cells, recombinant protein expression, therapeutic proteins, cell line development, vector engineering, site-specific integration, cis-regulatory elements, gene expression stability, cell engineering, growth-promoting factors, culture medium optimization, transcriptomics, proteomics, metabolomics, bioprocess optimization
- MeSH terms
- Animals, Biotechnology, Cricetulus, Genetic Vectors, Cricetinae, Humans, Recombinant Proteins, CHO Cells, Gene Targeting, Cell Culture Techniques, Cell Engineering
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