Research &
Development

The place where today’s new idea becomes tomorrow’s reality

A bright new idea or an intriguing problem? At PlasmidFactory’s R&D labs, we boldly enter uncharted territories every day. We are motivated to apply our scientific and technical expertise to continuous process optimization at every stage of the DNA production process. We solve problems, unravel new information, support customers, test the waters with new methodologies, or simply embark on radically new scientific avenues. In addition to our in-house R&D, we work in strategic partnership with research institutions and other companies, with whom we jointly drive innovation in the field of DNA production. Such collaborations have formed the groundwork for new knowledge in the field and yielded a multitude of significant publications.

Over more than two decades we have sought to develop innovative solutions to the challenges facing our customers. The expertise and experience acquired in that time have formed the basis for an innovative approach to every new challenge. This ethos is applied to each new project, continually breaking new ground together with our customers to shape the future of plasmid production.

R&D projects at PlasmidFactory encompass the entire plasmid DNA production chain starting, from strain and construct optimization through upstream bioprocess, to downstream purification strategies and, ultimately, DNA product analysis. Ongoing projects are currently developing engineered strains to increase plasmid DNA productivity per cell. We continually optimize fed-batch fermentation strategies for increased productivity. During the COVID pandemic, we successfully set up a large-scale plasmid DNA production process in record time. Recently, we tested our first single-use fermentation process, which will be transferred to the new GMP facility.

We critically test different purification platforms for both capacity and performance so that our DNA purification procedures are constantly aligned with the most stringent benchmarks. Our processes are designed and adapted to ensure that we deliver the highest degree of purity and reliability, features that our customers have become accustomed to over the years, while continuously seeking to improve our outputs at every level. We published one of the first in-house methods to quantify plasmid DNA isoforms and have developed a novel in-house method to measure critical process contaminants such as host cell DNA. Moreover, we have introduced NGS analysis to our processes to ensure the integrity of critical sequence elements such as ITR sequences (ITRRESCUE®).

We are currently working in close collaboration with industrial and academic partners in the following areas:

Plasmid application

  • Development of Next Generation Gene vectors, non-viral and free of antibiotic resistance genes (e.g. minicircles)
  • Plasmids and minicircles for production of mRNA, vaccines, and antibodies, among other products
  • Assessment of performance of linear vs circular DNA in diverse applications (e.g. transfection rate)
  • Production of dimeric plasmids (e.g. reporter gene vectors)

Viral vector production

  • Transient minicircle-based AAV production
  • Optimization of lentiviral vector systems

Plasmid stability

  • Investigation of the influence of various factors (plasmid size, concentration, storage buffer, containment) on long-term stability of plasmid DNA
  • Influence of freeze-thaw cycles on plasmid topology distribution

Plasmid quality control

  • Expanding the applications of capillary gel electrophoresis
  • Next generation sequencing

Process development

  • Process development for large scale and high quality (HQ and GMP) production of plasmid and minicircle DNA
  • Tangential flow filtration (TFF) of DNA
  • Fed-batch cultvation
  • Synthetic DNA / MIDGE® technology
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We continually optimize fed-batch fermentation strategies for increased productivity.

Insights

We indeed have a very fruitful and productive scientific collaboration with PlasmidFactory for more than 10 years now.

Prof. Dr. Michael Hudecek, Universitätsklinikum Würzburg/2023

Our Publications

PlasmidFactory regularly publishes specialist articles on plasmid and minicircle DNA. Relevant publications can be found here, or directly requested from us.

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Useful background information

The most important terms relating to minicircle DNA and plasmids explained in detail. Useful background information for smooth communication.

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