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Engineering of bacterial strains and vectors for the production of plasmid DNA

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Abstract

The demand for plasmid DNA (pDNA) is anticipated to increase significantly as DNA vaccines and non-viral gene therapies enter phase 3 clinical trials and are approved for use. This increased demand, along with renewed interest in pDNA as a therapeutic vector, has motivated research targeting the design of high-yield, cost-effective manufacturing processes. An important aspect of this research is engineering bacterial strains and plasmids that are specifically suited to the production of plasmid biopharmaceuticals. This review will survey recent innovations in strain and vector engineering that aim to improve plasmid stability, enhance product safety, increase yield, and facilitate downstream purification. While these innovations all seek to enhance pDNA production, they can vary in complexity from subtle alterations of the host genome or vector backbone to the investigation of non-traditional host strains for higher pDNA yields.

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Acknowledgment

Funding for this work was provided by the MIT-Portugal Program.

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  1. Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Room 66-425, Cambridge, MA, 02139, USA

    Diana M. Bower & Kristala L. J. Prather

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  1. Diana M. Bower
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  2. Kristala L. J. Prather
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Correspondence to Kristala L. J. Prather.

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Bower, D.M., Prather, K.L.J. Engineering of bacterial strains and vectors for the production of plasmid DNA. Appl Microbiol Biotechnol 82, 805–813 (2009). https://doi.org/10.1007/s00253-009-1889-8

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  • DOI: https://doi.org/10.1007/s00253-009-1889-8

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