ArticleMetabolic engineering2012
Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin.
Article in Metabolic engineering, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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.
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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.
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Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
- Chondroitin sulfate shapes the unfolded protein response in osteosarcoma to sustain cancer cell survival during ER stress.Cell death & disease · 2026Article
- Synthetic biology for heparin biomanufacturing.Bioresources and bioprocessing · 2026Review
- Multifaceted Heparin: Diverse Applications beyond Anticoagulant Therapy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Biosynthesis of animal-free recombinant chondroitin sulfate E using a functional chondroitin sulfotransferase in E. coli.Applied microbiology and biotechnology · 2024Article
- Synthesis of bioengineered heparin chemically and biologically similar to porcine-derived products and convertible to low MW heparin.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Improvement of the stability and catalytic efficiency of heparan sulfate N-sulfotransferase for preparing N-sulfated heparosan.Journal of industrial microbiology & biotechnology · 2023Article
- The 3-O sulfation of heparan sulfate proteoglycans contributes to the cellular internalization of tau aggregates.BMC molecular and cell biology · 2022Article
- Chemoenzymatic Synthesis of Homogeneous Heparan Sulfate and Chondroitin Sulfate Chimeras.ACS chemical biology · 2022Article
- Heterologous production of chondroitin.Biotechnology reports (Amsterdam, Netherlands) · 2022Review
- Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates.Science advances · 2021Article
- Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia.Thrombosis journal · 2021Review
- 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
- Efficient Synthesis of Heparinoid Bioconjugates for Tailoring FGF2 Activity at the Stem Cell-Matrix Interface.Bioconjugate chemistry · 2019Article
- The GAGOme: a cell-based library of displayed glycosaminoglycans.Nature methods · 2018Article
- Heparin: role in protein purification and substitution with animal-component free material.Applied microbiology and biotechnology · 2018Review
- Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR) Spectroscopy.Molecules (Basel, Switzerland) · 2018Review
- Recombinant Heparin-New Opportunities.Frontiers in medicine · 2018Review
- Optimization of bioengineered heparin/heparan sulfate production for therapeutic applications.Bioengineered · 2017Article
- Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors.Molecules (Basel, Switzerland) · 2017Article
- Engineered heparins as new anticoagulant drugs.Bioengineering & translational medicine · 2017Review
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9 authors at 4 institutions in 1 country.
Funding
Abstract
Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary.
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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.