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Rational engineering of Escherichia coli strains for plasmid biopharmaceutical manufacturing
Author(s) -
Gonçalves Geisa A. L.,
Bower Diana M.,
Prazeres Duarte M. F.,
Monteiro Gabriel A.,
Prather Kristala L. J.
Publication year - 2012
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201100062
Subject(s) - biopharmaceutical , plasmid , escherichia coli , dna vaccination , microbiology and biotechnology , recombinant dna , gene , biology , biochemical engineering , computational biology , genetics , engineering
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.