For the transfer of genetic information into the respective target cells, vectors based on plasmid DNA are used. In addition to the use as an active ingredient to complement genetic defects in the context of cell and gene therapy, immunization based on DNA, e.g. against pathogenic viruses or tumor tissue (genetic vaccination), the activation of new tissue formation or the support of tissue regeneration are further clinical fields of application of plasmid DNA. Here, the plasmids carry the gene sequences for the intracellular production of the encoded proteins.
Moreover plasmids also serve as starting material for the production of viral vectors (AAV, lenti etc.) and for the production of RNA. In particular, the production of plasmid DNA as a starting material for the production of RNA vaccines has gained in importance, especially in the contaxt of the COVID-19 pandemic, as RNA is considered a promising vaccine candidate for the prevention of certain virus infections and with the additional advantage of not integrating into the genome of the cell and thus remaining as a potentially effective molecule in a patient’s body in the long term.
PlasmidFactory (Bielefeld, Germany) has developed and established a process for the production of the corresponding plasmid DNA, which fulfills the requirements to be used as a starting material for production of such RNA used in clinical applications: High Quality Grade plasmid DNA. This plasmid DNA is produced in a special facility where starting from a characterized cell bank (RCB), the manufacturing process goes through various well-documented production steps. The HQ fermentation plant is spatially separated from purification (chromatography) in order to ensure that downstream processing of the sensitive DNA is not impaired by living contamination. The proprietary special purification process results in a high level of pure, supercoiled (ccc) plasmid monomers that meet the legal requirements to form a defined, homogeneous product which undergoes a series of quality controls for the cell bank and the plasmid prior to release.
In contrast to previously available methods, which were qualitatively and quantitatively sufficient for the production of plasmid DNA for research applications, now a process must be created through which plasmids can be produced in sufficient quantities as High Quality Grade material.
Due to the high quality requirements, this is a demanding challenge, which PlasmidFactory faces today both in the field of fermentation and chromatographic processing of the DNA product.
However, due to its expertise, PlasmidFactory plays a pioneering role here – paving the way for vaccine production.