Development of a highly productive and scalable plasmid DNA production platform

摘要: With the applications of DNA vaccines extending from infectious diseases to cancer, achieving most efficient, reproducible, robust, scalable, and economical production clinical grade plasmid is paramount medical commercial success this novel vaccination paradigm. A first generation process based on cultivation Escherichia coli in a chemically defined medium, employing fed-batch strategy, delivered reasonable volumetric productivities (500-750 mg/L) proved perform very well across wide range E. constructs upon scale-up at industrial scale. However, presence monosodium glutamate (MSG) formulation feed solution was found be potential cause variability. The development second process, medium excluding MSG, undertaken. Optimization studies, coding for HIV gag protein, resulted conditions that supported titers excess 1.2 g/L, while specific yields ranging 25 32 microg DNA/mg dry cell weight. When used supplies, demonstrated applicability two other 2,000-L bioreactors. This highly productive.