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Rational engineering of Escherichia coli strains for plasmid biopharmaceutical manufacturing

Author(s)
Gonçalves, Geisa A. L.; Bower, Diana Morgan; Prazeres, Duarte M. F.; Monteiro, Gabriel A.; Jones, Kristala L.
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Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
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Abstract
Plasmid DNA (pDNA) has become very attractive as a biopharmaceutical, especially for gene therapy and DNA vaccination. Currently, there are a few products licensed for veterinary applications and numerous plasmids in clinical trials for use in humans. Recent work in both academia and industry demonstrates a need for technological and economical improvement in pDNA manufacturing. Significant progress has been achieved in plasmid design and downstream processing, but there is still a demand for improved production strains. This review focuses on engineering of Escherichia coli strains for plasmid DNA production, understanding the differences between the traditional use of pDNA for recombinant protein production and its role as a biopharmaceutical. We will present recent developments in engineering of E. coli strains, highlight essential genes for improvement of pDNA yield and quality, and analyze the impact of various process strategies on gene expression in pDNA production strains. Keywords: Central metabolism; Escherichia coli; Metabolic engineering; Plasmid biopharmaceuticals; Strain engineering
Date issued
2011-09
URI
https://hdl.handle.net/1721.1/121771
Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Journal
Biotechnology Journal
Publisher
Wiley
Citation
Goncalves, Geisa A. L. et al. "Rational engineering of Escherichia coli strains for plasmid biopharmaceutical manufacturing." Biotechnology Journal 7, 2 (February 2012): 251-261 © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Version: Author's final manuscript
ISSN
1860-6768

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