A Consensus is Building Around Enzymatic DNA Synthesis

Enzymatic synthesis will power the future of synthetic biology, precision medicine, as well as DNA data storage

It was a great start to the year to present at the 40th Annual J.P. Morgan Healthcare Conference (JPM), talk to industry colleagues, and learn about the technology leaps and trends anticipated by both public and private industry leaders. Its conclusion also provides a great opportunity to reflect.

We were gratified to hear, for the first time at JPM, industry players announce programs involving enzymatic DNA synthesis. These announcements of investments in enzymatic synthesis development as an alternative to phosphoramidite chemistry validate our mission, beliefs and the last eight years of hard work on advancing this technology. Further, these moves serve as independent recognition of the opportunity we see ahead of us and the direction that the market is taking.

Synthetic DNA and RNA are essential to most life science workflows. Newer applications, like CRISPR and mRNA diagnostics and therapeutics, including vaccines, have increased the needs for these essential reagents. From basic discovery to developing new diagnostics and drugs to data storage and computing, the demand for synthetic nucleic acids will only grow.

Current synthetic DNA synthesis, based on 40-year old phosphoramidite chemistry technology, has been centralized under service providers that are encumbered by organic solvents, toxic waste, and delivery wait times. The COVID-19 pandemic revealed cracks in this outsourcing system, shining a light on the bottlenecks created by full dependency on third-party service providers. At a time when innovation to address the pandemic needed to accelerate, access to synthetic DNA encountered significant delays. It is clear that chemical synthesis and a centralized service model cannot address all the existing and emerging needs as well as the sustainability constraints of our industry.?

We founded DNA Script just eight years ago, developing a novel technology and expertise that is at the core of our mission and products, Enzymatic DNA Synthesis (EDS), and are the first to launch a commercial product (SYNTAX System, June 2021) based on this sustainable technology. We’ve already synthesized over 10 million nucleotides to date, and because our EDS is based on an aqueous process, it is a safer alternative for lab personnel to use and a greener solution than chemical synthesis. As a benchtop DNA printer, the SYNTAX System puts the power of workflow control and on-demand DNA in the hands of researchers, freeing their innovation from the constraints of outsourcing.?

Our customers and partners are using the SYNTAX System for a broad range of applications, including endpoint PCR, qPCR, NGS enrichment, CRISPR, protein engineering libraries and even gene synthesis. Their workflow, under their control, without waiting days or weeks for synthetic DNA orders to be delivered before proceeding with their research.?

At AGBT in 2020, we shared that our EDS technology had demonstrated the capability to produce scarless oligos 280 nt long. This proof of principle led to the commercialization of our first instrument and kits supporting synthesis of up to 96 oligos up to 60 nt in length with an equivalent or higher accuracy as chemical synthesis. We anticipate launching our next version of kits soon to enable SYNTAX users to synthesize longer oligos with modifications, including fluorophores, biotin and quencher labels.?

As the commercial leader of enzymatic synthesis, we are proud to have been selected to partner with companies on the world stage of developing deployable tools to combat the next pandemic, including Moderna and GE Research (DARPA programs). These are projects where both the traditional service model and phosphoramidite chemistry synthesis would not work, given its latency time, required environmental control, and handling and ventilation of hazardous chemicals. We’re also at the forefront of working with leaders on the DNA data storage front, including The Broad, Harvard, and Illumina (IARPA grant recipients) as well as Microsoft. Long data archiving is another example of an application where the use of the hazardous chemicals used in traditional phosphoramidite synthesis will likely not be acceptable for the technology industry leaders.?

While we forge ahead with our mission, we are confident that the EDS technology at the core of DNA Script’s business will grow to become the sustainable go-to method for producing high quality synthetic nucleic acids, democratizing access, and accelerating innovation.?

We see a consensus building. Enzymatic DNA Synthesis is the future.