Insights from Ansa co-founders about how a paper in Nature Biotechnology catalyzed an approach to nurturing untouched biological ambitions
In 2018, Ansa co-founders Dan-Lin Arlow, “a computer kid” growing up, and Sebastian Palluk, an athlete turned biologist, published “De novo DNA synthesis using polymerase-nucleotide conjugates” in Nature Biotechnology. Although the publication only reported synthesis of a short 10-base oligonucleotide using their novel approach, it was groundbreaking because it was the first demonstration of a new method for writing DNA in over 30 years, and since it was powered by enzymes rather than phosphoramidite chemistry, it would likely not have the same fundamental limitations that have stagnated the chemical method for so long.
Soon after that, Dan was contacted by Ansa’a third co-founder, Jared Ellefson, who had been focused on directed evolution of novel polymerase enzymes and was very familiar with the frustrations of needing to build his own DNA from scratch. They already shared a mutual scientific admiration for each other through publications and quickly realized the magic that was possible in combining the new enzymatic DNA synthesis method with the latest innovations in directed evolution.
That Nature Biotechnology paper also gave the scientists a path to their pre-seed round of funding; just enough to allow them to get incubator space near UC Berkeley and the bare minimum equipment to make progress. Within 5 months, Jared had a new high-throughput technique for engineering terminal deoxynucleotidyl transferase (TdT) up and running. Where most people would design and test dozens of variants of TdT at a time, he had invented a method to test millions of mutants of TdT in an afternoon. Combining improvements to the TdT enzyme with new linker chemistry generated novel conjugates that proved that an enzymatic process could achieve significantly higher coupling efficiencies compared to the gold standard phosphoramidite process. They were well on their way to creating a revolutionary new enzymatic approach to provide uncompromised, rapid access to the most complex biological sequences. The goal was to remove the boundaries established by other vendors, giving scientists the ability to work more freely in pursuit of their dreams rather than taper down their aim to fit within the confines of existing technology.
Despite these early successes, the small team was met with the traditional disbelief from members of the community who didn’t see their technology as scalable. Time and time again, the decades-long established phosphoramidite chemistry remained untouchable in the minds of some. But often, game-changing developments are influenced by someone being told they can’t do something.
Fast forward about 5 years and Ansa’s revolutionary approach has moved from proof-of-concept to adoption in prominent institutions that can now tackle scientific ambitions without the DNA compromise they once faced. Scientists that were previously hindered by what was available to them are now making progress in areas spanning cell therapy, gene therapy, CRISPR based applications, vaccine development and so much more. By providing access to DNA like never before, we aim to enable scientists to change the boundaries of biology as we currently know it.