Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach
Fed-batch cultures of Chinese Hamster Ovary cells have been used to produce high quantities of biotherapeutics, particularly monoclonal antibodies. However, a growing number of next-generation biotherapeutics, such as bi-specific antibodies and fusion proteins, are difficult to express using standar...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.658325/full |
| _version_ | 1823944206395113472 |
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| author | James S. Donaldson Matthew P. Dale Susan J. Rosser |
| author_facet | James S. Donaldson Matthew P. Dale Susan J. Rosser |
| author_sort | James S. Donaldson |
| collection | DOAJ |
| description | Fed-batch cultures of Chinese Hamster Ovary cells have been used to produce high quantities of biotherapeutics, particularly monoclonal antibodies. However, a growing number of next-generation biotherapeutics, such as bi-specific antibodies and fusion proteins, are difficult to express using standard fed-batch processes. Decoupling cell growth and biotherapeutic production is becoming an increasingly desired strategy for the biomanufacturing industry, especially for difficult-to-express products. Cells are grown to a high cell density in the absence of recombinant protein production (the growth phase), then expression of the recombinant protein is induced and cell proliferation halted (the production phase), usually by combining an inducible gene expression system with a proliferation control strategy. Separating the growth and production phases allows cell resources to be more efficiently directed toward either growth or production, improving growth characteristics and enhancing the production of difficult to express proteins. However, current mammalian cell proliferation control methods rely on temperature shifts and chemical agents, which interact with many non-proliferation pathways, leading to variable impacts on product quality and culture viability. Synthetic biology offers an alternative approach by strategically targeting proliferation pathways to arrest cell growth but have largely remained unused in industrial bioproduction. Due to recent developments in microbial decoupling systems and advances in available mammalian cell engineering tools, we propose that the synthetic biology approach to decoupling growth and production needs revisiting. |
| first_indexed | 2024-12-17T08:07:11Z |
| format | Article |
| id | doaj.art-17249185bd604cc39281b373cf2e712e |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-17T08:07:11Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-17249185bd604cc39281b373cf2e712e2022-12-21T21:57:19ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-06-01910.3389/fbioe.2021.658325658325Decoupling Growth and Protein Production in CHO Cells: A Targeted ApproachJames S. DonaldsonMatthew P. DaleSusan J. RosserFed-batch cultures of Chinese Hamster Ovary cells have been used to produce high quantities of biotherapeutics, particularly monoclonal antibodies. However, a growing number of next-generation biotherapeutics, such as bi-specific antibodies and fusion proteins, are difficult to express using standard fed-batch processes. Decoupling cell growth and biotherapeutic production is becoming an increasingly desired strategy for the biomanufacturing industry, especially for difficult-to-express products. Cells are grown to a high cell density in the absence of recombinant protein production (the growth phase), then expression of the recombinant protein is induced and cell proliferation halted (the production phase), usually by combining an inducible gene expression system with a proliferation control strategy. Separating the growth and production phases allows cell resources to be more efficiently directed toward either growth or production, improving growth characteristics and enhancing the production of difficult to express proteins. However, current mammalian cell proliferation control methods rely on temperature shifts and chemical agents, which interact with many non-proliferation pathways, leading to variable impacts on product quality and culture viability. Synthetic biology offers an alternative approach by strategically targeting proliferation pathways to arrest cell growth but have largely remained unused in industrial bioproduction. Due to recent developments in microbial decoupling systems and advances in available mammalian cell engineering tools, we propose that the synthetic biology approach to decoupling growth and production needs revisiting.https://www.frontiersin.org/articles/10.3389/fbioe.2021.658325/fullbiomanufacturingsynthetic biologydecoupling production from growthCRISPR/Cas9CHO cell culture |
| spellingShingle | James S. Donaldson Matthew P. Dale Susan J. Rosser Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach Frontiers in Bioengineering and Biotechnology biomanufacturing synthetic biology decoupling production from growth CRISPR/Cas9 CHO cell culture |
| title | Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach |
| title_full | Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach |
| title_fullStr | Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach |
| title_full_unstemmed | Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach |
| title_short | Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach |
| title_sort | decoupling growth and protein production in cho cells a targeted approach |
| topic | biomanufacturing synthetic biology decoupling production from growth CRISPR/Cas9 CHO cell culture |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.658325/full |
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