Genetic drug development has made great strides in more complex DNA molecules. While the long sequences of these synthetic DNAs are key to developing gene and cell therapies, as well as antibodies and other biological drugs, their length also poses problems. The popular method of synthesizing DNA is a decades-old process that uses harsh chemicals to destroy DNA strands as they are made. The longer you go, the more damage, says Daniel Lin-Arlow, co-founder and CEO of Ansa Biotechnologies.
“Chemistry has given us all the biotech wonders we have today, and I have a lot of respect for that,” Lin-Arlow said. “But nature can make very long molecules without damaging them.”
Ansa’s DNA synthesis technology uses enzymes. This method can make long, complex sequences without damaging them, Lin-Arlow said. Emeryville, California-based Ansa has been developing the technology for the past four years. The startup, which is now gearing up to showcase its enzymatically synthesized product to potential customers, has raised $68 million to scale operations and launch its product.
Series A financing Announce Led by Northpond Ventures on Monday.
While chemical synthesis has been around since the 1960s, enzymatic synthesis has a longer history. The key enzyme terminal deoxynucleotidyl transferase (TdT) was first discovered in 1959, says Lin-Arlow. The challenge with using the enzyme is controlling it—adding a base to the sequence and then stopping the enzyme. TdT can be controlled by a “reversible terminator,” a nucleotide that prevents the addition of extra bases to the sequence. But Lin-Arlow says this approach is challenging because TdT doesn’t like to accept nucleotides with these blocking groups.
Ansa developed a method to control TdT without reversible terminators. The company’s technology takes the TdT enzyme and uses a linker to attach nucleotides to it. Since the enzyme has only one nucleotide, only one can be added. After this nucleotide is added, the enzyme stops, preventing other conjugates from adding their molecules. To further extend the sequence, the linker is cleaved to release the TdT enzyme, enabling the process to repeat.
“You want the enzyme to add only one base, not zero, not two,” Lin-Arlow said. “Equally important is [the enzyme does] Does not damage DNA. “
Ansa’s technology grew out of graduate research at UC Berkeley by Lin-Arlow and company co-founder Sebastian Palluk. In 2018, they were both co-authors of the paper post This enzymatic method is described in Nature Biotechnology.
Lin-Arlow said he has been in discussions with potential customers to try out Ansa technology, serve these research-stage companies, and build sequences for them that they struggle to get from other suppliers. Beyond biopharma, Lin-Arlow said potential users of the technology include industrial biotech companies that are using synthetic biology to engineer microbes to produce chemicals.The company has Partner with Microsoft In collaboration to develop enzymatic reagents that can be used for DNA-based storage. The idea is to store digital information in the sequence of DNA molecules as a way to archive the information.
“One of the big advantages of doing this is that DNA, stored under the right conditions, can be stored for thousands of years,” Lin-Arlow said. But “the immediate focus is on pharmaceuticals and other synthetic biology applications”.
Although chemical DNA synthesis has been around for decades, it has seen some innovations. Twist Bioscience’s technology platform “writes” DNA on a silicon chip, an approach that miniaturizes the process and brings precision, automation and scalability to the chemistry of DNA synthesis. For the fiscal year ended September 30, 2021, Twist reported synthetic DNA product sales of $132.3 million, an increase of nearly 47% from the previous fiscal year.
When it comes to enzymatic synthesis, Ansa will compete with other startups that are also raising capital. DNA Script’s contribution to enzymatic synthesis is a benchtop instrument that laboratories can use to print synthetic nucleic acids on demand.In January, the France-based company shut down the second term Its $200 million Series C financing.San Diego-based Molecular Assemblies is advancing its enzyme technology toward commercialization and shuts down $25.8 million The push was backed by a Series B funding round last month.
Lin-Arlow believes Ansa’s method is superior to other enzymatic synthesis techniques. Competitors still use chemistry to block the blocking step of the TdT enzyme, he said. Ansa’s process is entirely based on enzymes, using different enzymes to stop the process. Ansa’s approach should also be cheaper, Lin-Arlow said. He explained that while the raw materials for chemicals may be cheaper than enzymes, the cost savings will come from streamlining the manufacturing process.
Ansa raised pre-seed funding in late 2018, the same year the startup’s research was first published, Lin-Arlow said.company $9.2 million closed In 2020, this funding represents both pre-seed and seed funding. Ansa said it has raised a total of $82 million to date, including the Series A round. Other participants in the latest funding round include new investors RA Capital Management, Blue Water Life Science Advisors, Altitude Life Science Advisors, Fiscus Ventures, PEAK6 Strategic Capital, Carbon Silicon, Codon Capital. They were joined by early investors Mubadala Capital, Humboldt Fund, Fifty Years and Horizons Ventures.
Image via Ansa Biotechnologies
