ArticleMolecular biotechnology2014
Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers.
Article in Molecular biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- Eicosadienoic acid enhances antibody production in CHO cells by prolonging culture longevity and attenuating apoptosis.AMB Express · 2026Article
- Impact of keto leucine and isoleucine on CHO cell central carbon metabolism and performance in fed-batch and steady-state perfusion.Frontiers in bioengineering and biotechnology · 2026Article
- AAV-Based Gene Therapy: Opportunities, Risks, and Scale-Up Strategies.International journal of molecular sciences · 2025Review
- A novel dual-epigenetic inhibitor enhances recombinant monoclonal antibody expression in CHO cells.Applied microbiology and biotechnology · 2024Article
- Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis.Frontiers in bioengineering and biotechnology · 2024Article
- Triple Space-Time Yield in Discontinuous Antibody Biomanufacturing by Combination of Synergetic Process Intensification Strategies.Bioengineering (Basel, Switzerland) · 2023Article
- Effects and mechanism of small molecule additives on recombinant protein in CHO cells.Applied microbiology and biotechnology · 2023Review
- Protein production from HEK293 cell line-derived stable pools with high protein quality and quantity to support discovery research.PloS one · 2023Article
- Rapid intensification of an established CHO cell fed-batch process.Biotechnology progress · 2022Article
- Digital Twins and Their Role in Model-Assisted Design of Experiments.Advances in biochemical engineering/biotechnology · 2021Article
- Article
- Methylthioadenosine (MTA) boosts cell-specific productivities of Chinese hamster ovary cultures: dosage effects on proliferation, cell cycle and gene expression.FEBS open bio · 2020Article
- Pre-stage perfusion and ultra-high seeding cell density in CHO fed-batch culture: a case study for process intensification guided by systems biotechnology.Bioprocess and biosystems engineering · 2020Article
- Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System.Analytical chemistry · 2020Article
- Increased MSX level improves biological productivity and production stability in multiple recombinant GS CHO cell lines.Engineering in life sciences · 2020Article
- High-Throughput Screening Identifies Two Novel Small Molecule Enhancers of Recombinant Protein Expression.Molecules (Basel, Switzerland) · 2020Article
- Immortalizing Mesenchymal Stromal Cells from Aged Donors While Keeping Their Essential Features.Stem cells international · 2020Article
- Screening Naturally Occurring Phenolic Antioxidants for Their Suitability as Additives to CHO Cell Culture Media Used to Produce Monoclonal Antibodies.Antioxidants (Basel, Switzerland) · 2019Article
- The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity.International journal of molecular and cellular medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Improving the productivity of a biopharmaceutical Chinese hamster ovary (CHO) fed-batch cell culture can enable cost savings and more efficient manufacturing capacity utilization. One method for increasing CHO cell productivity is the addition of histone deacetylase (HDAC) inhibitors to the cell culture process. In this study, we examined the effect of valproic acid (VPA, 2-propylpentanoic acid), a branched-chain carboxylic acid HDAC inhibitor, on the productivity of three of our CHO cell lines that stably express monoclonal antibodies. Fed-batch shake flask VPA titrations on the three different CHO cell lines yielded cell line-specific results. Cell line A responded highly positively, cell line B responded mildly positively, and cell line C did not respond. We then performed factorial experiments to identify the optimal VPA concentration and day of addition for cell line A. After identifying the optimal conditions for cell line A, we performed verification experiments in fed-batch bioreactors for cell lines A and B. These experiments confirmed that a high dose of VPA late in the culture can increase harvest titer >20 % without greatly changing antibody aggregation, charge heterogeneity, and N-linked glycosylation profiles. Our results suggest that VPA is an attractive and viable small molecule enhancer of protein production for biopharmaceutical CHO cell culture processes.
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