ArticleBiotechnology journal2015
Optimization of bioprocess conditions improves production of a CHO cell-derived, bioengineered heparin.
Article in Biotechnology journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 35 citations in OpenAlex.
- Synthetic biology for heparin biomanufacturing.Bioresources and bioprocessing · 2026Review
- Progress in fed-batch culture for recombinant protein production in CHO cells.Applied microbiology and biotechnology · 2023Review
- Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia.Thrombosis journal · 2021Review
- Bioengineered production of glycosaminoglycans and their analogues.Systems microbiology and biomanufacturing · 2021Article
- ZNF263 is a transcriptional regulator of heparin and heparan sulfate biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants.Molecules (Basel, Switzerland) · 2019Article
- Optimization of Key Factors in Serum Free Medium for Production of Human Recombinant GM-CSF Using Response Surface Methodology.Iranian journal of pharmaceutical research : IJPR · 2019Article
- Recombinant Heparin-New Opportunities.Frontiers in medicine · 2018Review
- Engineered heparins as new anticoagulant drugs.Bioengineering & translational medicine · 2017Review
- Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c.The Journal of biological chemistry · 2017Article
- Heparin: Past, Present, and Future.Pharmaceuticals (Basel, Switzerland) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Heparin is the most widely used anticoagulant drug in the world today. Heparin is currently produced from animal tissues, primarily porcine intestines. A recent contamination crisis motivated development of a non-animal-derived source of this critical drug. We hypothesized that Chinese hamster ovary (CHO) cells could be metabolically engineered to produce a bioengineered heparin, equivalent to current pharmaceutical heparin. We previously engineered CHO-S cells to overexpress two exogenous enzymes from the heparin/heparan sulfate biosynthetic pathway, increasing the anticoagulant activity ∼100-fold and the heparin/heparan sulfate yield ∼10-fold. Here, we explored the effects of bioprocess parameters on the yield and anticoagulant activity of the bioengineered GAGs. Fed-batch shaker-flask studies using a proprietary, chemically-defined feed, resulted in ∼two-fold increase in integrated viable cell density and a 70% increase in specific productivity, resulting in nearly three-fold increase in product titer. Transferring the process to a stirred-tank bioreactor increased the productivity further, yielding a final product concentration of ∼90 μg/mL. Unfortunately, the product composition still differs from pharmaceutical heparin, suggesting that additional metabolic engineering will be required. However, these studies clearly demonstrate bioprocess optimization, in parallel with metabolic engineering refinements, will play a substantial role in developing a bioengineered heparin to replace the current animal-derived drug.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.