Rapid Process Development for High Yield Plasmid DNA Fed-batch Fermentation

How to reduce plasmid-mediated metabolic burden for higher yields.
Nov 01, 2009
Volume 22, Issue 11


The temperature-inducible fermentation process has been successfully scaled-up to 300 L and used for GMP production of DNA vaccine plasmids. Fermentation cells are compatible with a variety of vectors,6–8 lysis,9 and downstream purification strategies.10–11 This low metabolic burden process is ideal as a generic plasmid DNA production platform to produce previously unstable and toxic plasmid DNA, as well as optimized plasmids at high yields in standard host strain DH5α, thus eliminating the need to use specialized stabilizing host strains. Contract manufacturers can use the base process with simple defined process optimization steps if necessary, to produce a wide range of customer-developed plasmids.


We thank Sheryl Anderson, Sarah Langtry, Justin Vincent, and Angela Schukar for their tireless efforts cleaning, batching, and operating fermenters. This paper described work supported by NIH grant R44GM072141.

James A. Williams is the vice president of research and development, Clague P. Hodgson is the president, and Aaron E. Carnes is the director of process development, all at Nature Technology Corporation, Lincoln, NE, 402.472.6530,


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