(307c) High Titer Production of Plasmid DNA in Disposable Fermentors

The production of plasmid DNA (pDNA) is a key feature in many of the in-vitro expressed biologics that represent the next generation of treatment options for patients. The material required for these programs is produced in E. coli which is then harvested and lysed to recover the pDNA. The fermentation process to produce pDNA in E. coli is a well-established practice and has been widely reported in literature. What has changed in recent years is the availability of disposable fermentors which can be used to produce pDNA in E. coli. The limitations of a disposable fermentor, including lower power input and limited back pressure than stainless vessels, results in the need to adapt the fermentation process which can lead to dramatically lower pDNA titers. In order to recoup the production losses, we have modified the stainless fermentation process to fit disposable systems and have further optimized the system within the control capabilities of the disposable system to enhance production. Details of the experimental methods and results will be discussed.