DNA synthesis News, Reviews & Resources

Touchlight Genetics and DNA Script have closed major venture financing rounds in the last month as investor excitement mounts over the next generations of DNA manufacturing. DNA Script made a big splash in Paris this week as it raked in €142M in Series C funding. The company will ramp up the commercialization of its benchtop DNA printer, which is designed to produce custom DNA molecules for life sciences labs in a fraction of the time that it takes to source from central suppliers. DNA Script’s fundraising came hot on the heels of a €60M (£50M) investment into Touchlight Genetics in the UK last month, which took its total Series B winnings to €108M (£92M). Touchlight manufactures a form of synthetic DNA called doggybone DNA (dbDNA) for use in DNA vaccines and gene therapies. This process is easier and faster than bacterial fermentation, the traditional production method for DNA used in advanced therapies. The Covid-19 pandemic has been accompanied by a boom in private investments in the biotech industry worldwide. As demand surges for regenerative medicine treatments, diagnostics, and more efficient manufacture of cell and gene therapies, the race is on to supply DNA, the backbone of many of these technologies. “DNA is a critical element in a lot of life sciences work and therefore everyone is interested in ensuring a broad base of available solutions that can secure the quality and affordability of supply,” said Joško Bobanović, an industrial biotechnology-focused Partner at Sofinnova Partners, an early investor in DNA Script. For decades, custom DNA molecules used in life sciences research have been made by central providers using chemical methods. The disadvantages of this model are that suppliers require large facilities and toxic chemicals to synthesize DNA, and can suffer disruption during times such as a pandemic. There has been soaring investor interest in players that can overcome the bottlenecks of DNA supplies. One approach in the spotlight is synthesizing DNA with enzymes, of which DNA Script is one of the leading players. A benefit of enzymatic DNA synthesis is that it doesn’t need the large quantities of toxic chemicals used in traditional chemical synthesis. This makes it environmentally safer and able to be used at a smaller scale. “DNA Script’s solution is totally sustainable, uses ambient conditions, and can be used in environments as simple as a kitchen,” said Bobanović. DNA Script’s DNA printers could reduce the need for external suppliers. Instead, they grant each user the ability to synthesize their own DNA. This could benefit firms developing precision medicine approaches as the users can have a quick, reliable stream of DNA molecules vital for diagnostics, genomics, and other lab techniques involved in precision medicine. “These innovative labs can make custom synthetic oligos on demand to accelerate the iterative design-print-test cycle essential to research and development pipelines to make new discoveries in less time,” said Thomas Ybert, co-founder and CEO of DNA Script. Touchlight Genetics, meanwhile, wants to revolutionize the production of DNA used in treatments such as mRNA vaccines, DNA vaccines, and gene therapy. This type of DNA is manufactured via a technique called DNA amplification, where a template DNA molecule is copied on a large scale. This traditionally takes place in bacterial cultures, however, the process is slow and requires the use of antibiotic resistance genes to filter out the right bacteria, a tactic that is becoming tightly regulated as antibiotic-resistant superbugs increase in prevalence. “The significant increase in demand from nucleic acid medicines, viral vectors, cell therapy, and genome editing in recent years has placed significant strain on capacity and thus has impacted turnaround times,” said Tommy Duncan, Chief Business Officer at Touchlight. Touchlight’s DNA amplification approach copies the DNA template using enzymes and without needing bacterial fermentation. This setup requires less time to manufacture dbDNA and avoids the use of antibiotic resistance genes, making the process safer. In addition to manufacturing services, Touchlight is developing its own DNA vaccines, including one against Covid-19. “We see [Touchlight’s] technology as complementary to ours and can envision fully integrated and automated workflows for cell and gene therapy manufacturing, enabling truly personalized medicine for instance,” said Ybert. There is still a big limitation in the DNA manufacturing industry: making long DNA molecules without the use of a template. Synthetic biology is advancing fast, and our ability to write genomes has lagged behind our ability to sequence them. Molecules made via chemical synthesis typically have an upper size limit of a few hundred base pairs due to a high error rate. Longer DNA molecules of thousands of base pairs -- which can contain whole genes or even genomes -- must be painstakingly assembled from smaller ones at a high cost. “The industry is good at making fairly small numbers of relatively short DNA sequences at low yield,” said Mike Daniels, Head of Product Management at the UK firm Evonetix. “This is fine for PCR and okay for constructing libraries for probes, barcodes, CRISPR editing, etc. But the future of engineering biology is going to need much greater numbers of different sequences and they are going to need to be a lot longer.” There are many startups aiming to bridge the gap with state-of-the-art automation, enzymatic synthesis, or both. For instance, Evonetix raised €27M (£23M) last year to fund the development of a microchip to boost the accuracy of DNA synthesis. And the Austrian firm Ribbon Biolabs managed to synthesize DNA molecules of over 10,000 base pairs with its enzymatic process in May this year. “Once you can easily make long, accurate DNA, the applications are huge,” said Daniels. He added that, combined with artificial intelligence-guided research tools such as DeepMind’s Alpha-Fold, “the ability to apply biology to some of the world’s biggest challenges in food, medicine, and fuel becomes a far more tangible prospect.” The release of the United Nations’ climate change report this week has hammered home the progress needed to kick our addiction to fossil fuels. The EU is keen to foster a circular bioeconomy to tackle the enormous challenge, but key technological advances are needed to make this goal economically feasible. With access to large pools of DNA from DNA Script’s machines, fast amplification with Touchlight’s technology, and affordable sources of long custom DNA molecules, synthetic biology researchers could become a growing part of the solution.

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