Production of plasmid DNA for pharmaceutical use.

The concept of curing diseases at the genetic level was already introduced in the 1970s, but only the evolution of molecular biology and tools for genetic manipulation brought the idea into labs and clinics during the last 16 years. Viral and non-viral vectors and delivery systems were developed to transfer therapeutic genes into the target cells. In the case of non-viral approaches plasmid DNA has become a very promising gene delivery vector because it can easily be genetically manipulated and produced by cultivation of plasmid harbouring Escherichia coli and subsequent downstream processing, thus making production easy in comparison to other gene delivery vectors. Another advantage in using plasmid DNA is the low risk of immunogenic reactions and oncogen activation that can arise while using viral vectors. This review describes the recent development in plasmid manufacturing ranging from bacterial cultivation in batch and fedbatch mode to produce plasmid-bearing E. coli over cell lysis and subsequent purification to storage, application, and process and quality control.