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Startup Molecular Assemblies Developing Novel Enzymatic DNA Synthesis Tech

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NEW YORK (GenomeWeb) – As it continues to refine a novel enzymatic DNA synthesis technology for the production of long, high-fidelity DNA sequences, startup Molecular Assemblies is getting ready for a $2.5 million Series A financing round it expects will carry it to its first industry partnership.      

Founded by CEO Curt Becker and CSO William Efcavitch, two of Applied Biosystems' earliest team members, Molecular Assemblies is built around a technology dubbed EcoDNA, which the company claims holds significant advantages over classical chemical DNA synthesis.

When automated DNA sequencing became available in the mid-1980s, Becker said, the maximum length of a sequence that could be generated was about 150 nucleotides. "The state of the art today," he added, "is 150-mer. That's the limit and it's been with us for 30 years."

The key issue with the widely used phosphoramidite-based method of DNA synthesis, Becker explained, is its reliance on harsh chemicals that can damage DNA even as it is being synthesized. As a result, it is challenging to produce long sequences and the synthesis process often has to be repeated to ensure high-quality DNA.

In these kinds of situations, "end users don't know what they are going get and when they are going to get it," he said. "If the synthesis doesn't work well the first or second time, it might take a month to six weeks to get a product you were expecting in two weeks. It's hard to schedule a workflow around that kind of lack of reliability."

In contrast, the EcoDNA method requires no acids, bases, or hazardous chemicals, Becker said. Essentially, the technology involves binding a deoxynucleotide triphosphate (dNTP) onto a solid support and the introduction of the DNA polymerase terminal deoxynucleotidyl transferase (TdT) to add nucleotides.

Importantly, the dNTP monomers are designed to remain substrates for TdT, include a terminator moiety to ensure that only a single nucleotide is added per cycle, and that the terminator group is stable and removable.

"Everything is done in water, everything is done at neutral pH, everything is done in a very biological-like system," Becker said.

The technology is covered by US patent No. 8,808,989, which was granted in August 2014.

To date, Molecular Assemblies has successfully created A, C, G, and T monomers that act as TdT substrates, with A and G "showing a very good, high level of termination," he noted. A, C, and G, meanwhile, are showing easy removal of their terminator groups.

The company expects to have completed work on the nucleotide analogs and be able to manually synthesize sequences longer than 150-mers — ideally up to 300-mers — consistently and reliably by early 2016. At that point, Molecular Assemblies expects to start forming pilot deals to demonstrate that EcoDNA can be easily incorporated into potential partners' automated processes.

Because the EcoDNA technology is "instrument agnostic," Becker said that he anticipates that this will be a relatively straightforward process and that Molecular Assemblies will be able to find its first licensee for the technology, initially in the area of gene synthesis, by late 2016 or early 2017.

He added that rather than compete with the big players that currently dominate the gene synthesis market, Molecular Assemblies aims to broadly license its technology. "In the long run, there are other market segments we can address [such as RNA synthesis] … and the emerging DNA therapeutics market," he noted. "We'll develop business models for those as we progress."

Laying the groundwork for its planned industry partnerships, however, will require additional funding. And while Molecular Assemblies has been able to thus far operate largely on grants from the National Science Foundation and the National Institutes of Health, expanding its research team from its current single chemist to a planned six or seven will require outside investment.

To that end, Molecular Assemblies is in the process of closing a small round of seed financing and aims to raise $2.5 million in a Series A later this year, Becker said. And if the company meets its goals, it expects to be revenue positive by mid- to late-2017.

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