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    Optimization of bioprocess conditions improves production of a CHO cell-derived, bioengineered heparin

    Author
    Baik, Jong Youn; Dahodwala, Hussain; Oduah, Eziafa; Talman, Lee; Gemmill, Trent R.; Gasimli, Leyla; Datta, Payel; Yang, Bo; Li, Guoyun; Zhang, Fuming; Li, Lingyun; Linhardt, Robert J.; Campbell, Andrew M.; Gorfien, Stephen F.; Sharfstein, Susan T.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    Date Issued
    2015-07-01
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Optimization of bioprocess conditions improves production of a CHO cell-derived, bioengineered heparin, J. Y. Baik, H. Dahodwala, E. Oduah, L. Talman, T. R. Gemmill, L. Gasimli, P. Datta, B. Yang, G. Li, F. Zhang, L. Li, R. J. Linhardt, A. M. Campbell, S.F. Gorfien, S. T. Sharfstein, Biotechnology Journal,10, 1067–1081, 2015.
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    URI
    https://hdl.handle.net/20.500.13015/5355; https://doi.org/10.1002/biot.201400665
    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.;
    Description
    Biotechnology Journal,10, 1067–1081; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    Wiley
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Biotechnology Journal; https://harc.rpi.edu/;
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