The Beginning: The Synthetic DNA Bottleneck

When Ansa's CSO Daniel Lin-Arlow started his PhD at UC Berkeley back in 2014, he wanted, in his own words, to “engineer cells to do useful stuff.” He dreamed of modifying cells to produce essential chemicals and medicines; gene synthesis wasn’t even on his radar. But this changed after seeing his lab mates struggle to build their genetic constructs.

“You could design tens of constructs in an afternoon, and then you had to wait a month to see if they worked,” Lin-Arlow told me. He recounts the labor put into cloning and manipulating DNA sequences and the frustration most molecular biologists working in the 2010s can relate to. Why can’t we just print out all of the sequences we need to engineer cells? He traced the root cause to the limitations of the dominant phosphoramidite chemistry used to produce oligonucleotides, which are assembled together to make synthetic DNA constructs. Lin-Arlow and his co-founder Sebastian Palluk decided to change that by founding Ansa Biotechnologies.

Ansa’s Technology and First Product Launch

Ansa Biotechnologies uses an enzymatic synthesis technology, harnessing the capabilities of terminal deoxynucleotidyl transferase (TdT), explained in detail in Lin-Arlow’s previous SynbioBeta article. This allows Ansa to directly synthesize sequences that are over 1,000 bases long, without sequence restrictions. While some ‘mainstream’ DNA synthesis companies have tremendously reduced costs and increased synthesis throughput, they can’t always reliably deliver complete orders, especially if the sequences  are “complex”. Ansa opens a new era of synthetic DNA complexity, enabling synthesis of the full range of sequences  found in real genomes, including: repeats, hairpins, extremes of GC content. “We provide access to difficult sequences but what we’re really doing is enabling engineering more interesting phenotypes and cellular functions,” Lin-Arlow highlighted. 

Ansa aims to relieve scientists from thinking and designing within the DNA synthesis constraints of their vendors but truly explore what genomic designs can attain. “The goal of my lab is 'bottom-up'  genome synthesis, which is currently focused on bacteriophage genomes. Recently, we began a collaboration on Mycobacterial phage genomes, whose high GC content created challenges in getting the DNA fragments either by PCR or synthetically,” Greg Lohman, Senior Scientist at New England Biolabs, said. “Ansa was able to provide the needed DNA fragments covering the whole genome quite rapidly, moving the project to the biological study phase much faster than we thought possible."

Ansa recently announced the commercial launch of the Ansa Clonal DNA and Ansa DNA Fragments products, making available direct synthesis of up to 600 bp sequences to customers. However, the most exciting update will come by the end of the year, when the company will make sequences up to 5,000 bp available to the public. Lin-Arlow hopes to increase this limit to more than 10,000 bp in 2025. “We are able to produce gigantic, 1,000 base oligos in less than 24 hours,” he added, clearly proud of the technical state Ansa has achieved. Beyond gene synthesis, the company will explore more application-focused products that push the boundaries of what synthetic biology can do.

Building A Winning Team and Ansa’s Place in the Ecosystem

What the company has achieved is the result of a great team effort. “We look for curious folks who are clear thinkers and respectful communicators,” Lin-Arlow commented on how he selects the people to join him in this journey. He also emphasized the importance of scientific rigor and a collaborative culture embedded in the startup.

Lin-Arlow closely follows the developments of synthetic biology. After all, he needs to know what his customers want to use his long DNA chunks for. When I asked him which areas he thinks have the most potential, he selected therapeutics for the near future and sustainability for longer-term impact. His time in Jay Keasling’s lab shaped the idea that microbes can be engineered to replace petrochemicals, while his interaction with pharmaceutical companies showed how synbio applications in areas such as cell therapies have a profound potential to treat disease. It is these applications that Ansa will want to tackle better with their synthetic DNA products. They have the ambition to let scientists experiment beyond protein-coding sequences that current DNA providers serve best, enabling routine engineering of  non-coding sequences like introns, promoters, and other regulatory elements.

What words of wisdom does a PhD-turned-founder have to share with prospective founders? Daniel Lin-Arlow urged them to prepare themselves with an emotional marathon. “Talking to real customers is the most valuable thing you can do— you get precious insights,” he noted. “However, you need to maintain a healthy balance of vision and conviction in what you do.” During our discussion, it was clear that Ansa and the company’s founders are driven by the goal of breaking the boundaries that DNA synthesis currently imposes.