SAN FRANCISCO – At SynBioBeta, the yearly showcase for the synthetic biology community, the supply of DNA for use in engineering cells is a top concern.
Molecular Assemblies is one of several companies here, joined by Twist Bioscience and SGI DNA, among others, who are working on ways to deliver precise constructs to customers in this space. The firm is working on an enzymatic approach to DNA synthesis different from the state of the art, phosphoramidite chemistry. If it can get an enzymatic process to work well, it could allow longer constructs, potentially as many as 1,000 base pairs, compared to 200 to 300 bp, lengths that Genscript and Twist say they can produce, respectively.
Though Molecular Assemblies can't yet create 150 bp-long constructs at the yield and purity that it wants, CEO Michael Kamdar and CSO Bill Efcavitch said the firm has come a long way in just a few years. Yesterday, the firm reported it raised $12.2 million in Series A financing, a round it had been working on since 2015. Kamdar said the firm has plans to raise even more, but money isn't the only indication of interest.
In years past, enzymatic synthesis was "really just a blip on the radar," Kamdar said. This year, Efcavitch was featured on the main stage in a panel discussion at SynBioBeta on DNA data storage, an application the firm's technology might enable. In addition, enzymatic synthesis was the topic of one of the breakout sessions, which also featured competitors Nuclera, DNA Script, Evonetix, Ansa Biotechnologies, and Kern Systems — a spinout from George Church's lab at Harvard Medical School that is focusing only on the DNA digital data storage space.
"In 2015, you'd have to convince people they might even think about synthesizing DNA with enzymes," Efcavitch said. "Today, everyone's like, 'When can I buy it?'"
One potential customer is Twist, whose CEO Emily Leproust said that she's following the enzymatic synthesis space. Though Twist uses a chemical approach to synthesis, Leproust said the firm's hardware is actually chemistry agnostic.
"There are eight different enzyme synthesis companies," Leproust said, "One of them is going to crack the code. It's a question of time. As soon as one has [a chemistry] that is better than ours, we'd be happy to be the first customer. But it has to be better."
Every enzymatic synthesis company is tackling the same essential problem: how to add exactly one base to an existing molecule. Molecular Assemblies will use its funding to develop its process, which uses reversible terminators and polymerases that don't require a template. The company’s patented method requires fewer steps than chemical synthesis, Efcavitch said, and is more environmentally sustainable.
But not everyone is as optimistic about the impact of enzymatic DNA synthesis. GenScript, a competitor in the DNA synthesis market, has worked with enzymatic synthesis but has abandoned it for commercial purposes. "I like the concept," said Cedric Wu, GenScript VP of R&D, but "there's no real advantage." Error rate and scalability are two challenges anybody working with enzymatic processes will have to deal with, he said.
Molecular Assemblies is not done raising money for its Series A, as the company expects to raise as much as $18 million to $20 million total within the next six months, Kamdar said. Growth was part of the reason the firm took so long to announce its Series A round (the firm said in 2015 it expected to close the round in 2016). "As we accelerated, we needed to raise more money," Kamdar said. "Obviously, the burn goes up accordingly." The firm is still growing: it now has 18 employees and is looking to grow to 20 or 22, Kamdar said, and is moving to a new San Diego facility operated by Alexandria Real Estate Equities. Alexandria's venture investment arm is one of Molecular Assemblies' funders.
Kamdar said the firm is focusing mostly on life sciences applications. But the new funding will help it give more attention to the area of digital data storage in DNA. "We've seen acceleration there, we'll put more resources on it for sure," he said. The process for writing DNA with the intention of storing is different than for writing DNA for use in biology. This application can tolerate more errors in the DNA, Efcavitch said, which allows the firm to think about what technologies might be used to read data at the time it will be accessed.
"We need to tailor the writing to anticipate how one might read out DNA info in the future," Efcavitch said. "I doubt they're going to use an Illumina sequencer."
Does that mean nanopore-based sequencing technology? "That would be a good thought," he said.