ArticleMetabolic engineering communications2021
Cell line development for continuous high cell density biomanufacturing: Exploiting hypoxia for improved productivity.
Article in Metabolic engineering communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- Using transcription and translation regulators to improve recombinant protein expression in CHO cells.Acta biochimica et biophysica Sinica · 2025Article
- Advancing ORFV-Based Therapeutics to the Clinical Stage.Reviews in medical virology · 2025Review
- Exploring synthetic biology for the development of a sensor cell line for automated bioprocess control.Scientific reports · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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Abstract
Oxygen deficiency (hypoxia) induces adverse effects during biotherapeutic protein production leading to reduced productivity and cell growth. Hypoxic conditions occur during classical batch fermentations using high cell densities or perfusion processes. Here we present an effort to create novel engineered Chinese hamster ovary (CHO) cell lines by exploiting encountered hypoxic bioprocess conditions to reinforce cellular production capacities. After verifying the conservation of the hypoxia-responsive pathway in CHO cell lines by analyzing oxygen sensing proteins HIF1a, HIF1β and VDL, hypoxia-response-elements (HREs) were functionally analyzed and used to create hypoxia-responsive expression vectors. Subsequently engineered hypoxia sensitive CHO cell lines significantly induced protein expression (SEAP) during adverse oxygen limitation encountered during batch fermentations as well as high cell density perfusion processes (2.7 fold). We also exploited this novel cell system to establish a highly effective oxygen shift as innovative bioprocessing strategy using hypoxia induction to improve production titers. Thus, substantial improvements can be made to optimize CHO cell productivity for novel bioprocessing challenges as oxygen limitation, providing an avenue to establish better cell systems by exploiting adverse process conditions for optimized biotherapeutic production.
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