Comparative phenotypic analysis of CHO clones and culture media for lactate shift

Hong, Jong Kwang; Nargund, Shilpa; Kyriakopoulos, Sarantos; Kim, Do Yun; Ang, Kok Siong; Leong, Dawn; Yang, Yuan Sheng; Lee, Dong-Yup

doi:10.1016/j.jbiotec.2018.07.042

Cited by 23 publications

(22 citation statements)

References 29 publications

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“…Our data suggest that the decreased consumption of glutamine due to the interventions (observed in both cell lines) contributed to the delayed transition to lactate consumption in the CHO EPO-Fc cells. This hypothesis agrees with previous studies evaluating the effect of glutamine concentration on lactate metabolism (Ghorbaniaghdam et al, 2014;Hong et al, 2018;Noh et al, 2017).…”

Section: Assessment Of the Individual Effects Of Blimp1 Overexpression Low Temperature And Nabu On Cell Growth R-protein Expression And Msupporting

confidence: 93%

Combined gene and environmental engineering offers a synergetic strategy to enhance r‐protein production in Chinese hamster ovary cells

Torres

Dickson

2021

Biotech & Bioengineering

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Environmental growth-inhibition conditions (GICs) have been used extensively for increasing cell-specific productivity (q P ) of Chinese hamster ovary (CHO) cells, with the most common being temperature downshift and sodium butyrate (NaBu) treatment. B lymphocyte-induced maturation protein-1 (BLIMP1) overexpression in CHO cells can also inhibit cell growth and increase product titers and q P . Given the similar responses, this study evaluated the individual and combined effects of BLIMP1 expression, low temperature, and NaBu treatment on culture performance, cell metabolism, and recombinant protein production of CHO cells. As expected, all three interventions decreased cell growth, arrested cells in G1/G0 cell cycle phase, and increased q P . However, CHO cells presented different responses when considering cell viability, recombinant gene expression, and cell metabolism that indicated differences in the molecular loci by which BLIMP1 and GICs generated higher productivities. Combinations of BLIMP1 expression and GICs acted synergistically to inhibit cell growth and maximize r-protein production, with the BLIMP1/NaBu condition leading to the most significant improvements in product titers and q P . This latter condition also proved to substantially increase product yields (up to 9.8 g immunoglobulin G1 [IgG1]/L and 2.2 g erythropoietin-Fc [EPO-Fc]/L) and q P (up to 179 pg/cell/day [pcd] for IgG1 and 30 pcd for EPO-Fc) in highdensity perfusion cultures. These findings offered mechanistic insights about the productivity-enhancing effects of BLIMP1 and GICs, as well as their complementarity for generating highly productive processes.

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Section: Assessment Of the Individual Effects Of Blimp1 Overexpression Low Temperature And Nabu On Cell Growth R-protein Expression And Msupporting

confidence: 93%

Combined gene and environmental engineering offers a synergetic strategy to enhance r‐protein production in Chinese hamster ovary cells

Torres

Dickson

2021

Biotech & Bioengineering

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“…40,41 While generally associated with the stationary phase, lactate consumption has been reported to occur prior to the stationary phase. 31,46,47 The shift has been reported for some cultures in association with declining availability of glucose 23,50,51 or glutamine, 8,41,52 both of which contribute to the pyruvate and lactate pools. 40,46 The switch to lactate consumption is also linked with reduced glycolytic flux, which is present predominantly in the stationary phase.…”

Section: Trends At the Pyruvate Branch Pointmentioning

confidence: 96%

“…Furthermore, growth trajectories cannot account for variations in metabolism due to cell line or growth media differences. 7,8 The dynamic three-phase model is improved by describing the metabolism of CHO cells according to metabolic trends. Within metabolic trends, biochemical variations, such an enzyme activity levels and metabolite concentrations, are captured.…”

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confidence: 99%

Metabolic trends of Chinese hamster ovary cells in biopharmaceutical production under batch and fed‐batch conditions

Rish

Drennen

Anderson

2021

Biotechnology Progress

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Extensive knowledge of Chinese hamster ovary (CHO) cell metabolism is required to improve process productivity and culture performance in biopharmaceutical manufacturing. However, CHO cells show a dynamic metabolism during culturing in batch and fed-batch bioreactors. CHO cell metabolism is generally described as taking place in three stages: exponential growth phase, stationary phase, and death phase. This review aims to summarize the trends of central metabolism for CHO cells during each stage. Additional insights into how culture conditions are related to phase transitions and force metabolic rewiring are provided. Understanding of CHO cell metabolism lends itself to improving culture qualities by, for example, identifying sources of toxic byproducts and pathways for cellular engineering. In summary, this review describes the changes in CHO cell central metabolism over the course of the culture.

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“…The major technological advancements along with the areas of application of CHO cell line development and engineering were discussed by Hong et al (2018a). The effects of media and clonal variation on lactate shift were studied for CHO cell culture, and it was shown that the clone exhibiting lactate shift produced less lactate in the exponential phase but 2-fold higher non-toxic alanine, thus leading to a better culture environment (Hong et al, 2018b). Comparative multi-omics analysis in another study indicated some physiological variations between CHO cells grown in the same media.…”

Section: Mammalian Cellsmentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

397

243

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Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

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Comparative phenotypic analysis of CHO clones and culture media for lactate shift

Cited by 23 publications

References 29 publications

Combined gene and environmental engineering offers a synergetic strategy to enhance r‐protein production in Chinese hamster ovary cells

Combined gene and environmental engineering offers a synergetic strategy to enhance r‐protein production in Chinese hamster ovary cells

Metabolic trends of Chinese hamster ovary cells in biopharmaceutical production under batch and fed‐batch conditions

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

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