How to fuel the genetic medicine revolution

With multiple COVID-19 mRNA vaccination regimes now well-established and the first generation of DNA vaccines emerging, we can safely claim that a new era in medicine has begun, says Karen Fallen, Chief Executive Officer, Touchlight DNA Services (TDS)

The concept of genetic medicines, which use DNA or RNA as a therapeutic agent, has been in development for decades. However, the pandemic has allowed them to show their true potential.

In the case of nucleic acid vaccines, this success has also provided much-needed clinical proof and unveiled a series of advantages compared with traditional vaccines, such as speedy manufacture and relative ease of adaptation.

Genetic medicines are much more than just vaccines against infectious diseases; the potential applications are vast, with prophylactics, gene therapies and cancer vaccines being the most advanced areas at the moment.

They not only bring a whole new approach to treatments, but also establish an entirely new supply chain, which is needed to ensure a reliable and plentiful supply of DNA.

Today’s mRNA vaccines are all built on plasmid DNA as the starting “ingredient.” It has indeed proven its worth, enabling the rapid production and availability of vaccines in only a matter of months — rather than the traditional timeline of years.

Karen Fallen

However, the anticipated potential of genetic medicines is likely to drive extraordinary demand for DNA in the coming years and decades. Plasmid DNA is already becoming a bottleneck and, despite many planned capacity expansions, the rapid and cost-effective scale-up of plasmid manufacturing is fundamentally constrained by its reliance on outdated technologies.

For this burgeoning industry, the key challenges to be addressed include long lead times and high capital costs. Traditionally, plasmid manufacture involves E. coli fermentation, which is slow, expensive and limited by lack of capacity.

Furthermore, batch failures are relatively common and, on occasion, antibiotic resistant genes might be present in the final product.

An alternative approach was taken by Touchlight, with an enzymatically amplified DNA vector called dbDNA (doggybone DNA). Since before the pandemic, we have been providing GMP dbDNA from our facilities in the UK and Spain on behalf of clients as well as for in-house programmes, including vaccines as well as cell/gene therapies.

During the last year and a half, we have seen demand for synthetic DNA triple; but, with our solution, we can effortlessly meet this demand.

Leveraging our ability to amplify any circular DNA template using proprietary in vitro enzymatic rolling circle method, dbDNA addresses most of the issues of traditional fermentation. Our approach outperforms traditional methods in terms of speed, scalability and safety, as well as reliability, but still in a cost-efficient manner.

Without any bacterial sequences, dbDNA offers superior safety, which also supports reliability by avoiding the challenges posed by the unexpected behaviour of bacterial sequences. Our process technologies can significantly increase fully purified yield by ten-fold … and there is scope for further improvement.

This large production capacity doesn’t come with major facility footprint either, as the benchtop scale of the dbDNA manufacturing technology is only a fraction of the space required by conventional bioreactor-based plasmid DNA manufacture.

This is partly because of the lack of need for highly specialised tools and technologies, and the fact that the technology used allows greater control over the full process. Together, these factors enable mass production at a truly global scale.

In addition, transferring our process globally is a relatively easy and fast process, which not only enables straightforward capacity expansion, but also the relocation to other countries or even continents.

Plasmid DNA-based genetic medicine has already shown great success, but this is still a young industry. Now is the time to broaden the horizon and see how we can make DNA in better and more efficient ways.

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