German biotech launches with ‘seamless’ gene editing platform built on evolving enzymes

16 Mar 2023
endpts.com
Gene Therapy
Seamless Therapeutics has launched with €11.8 million (roughly $12.5 million) in seed funding to build out a gene editing platform. As more and more gene editing techniques are being developed — starting with CRISPR/Cas9 to base and prime editing, and more recently, PASTE — Seamless is trying to evolve, literally, an approach that dates back decades. The Dresden, Germany-based startup is developing so-called “designer recombinases” that can potentially edit large chunks of genes. Recombinases are enzymes that can excise, invert, or even insert a DNA sequence, but typically they only work via very specific target sequences. However, by continuously evolving these recombinases, Seamless is trying to develop recombinases that work at the sequences it wants — those that are found in human genes. The biotech stems from Frank Buchholz’s lab at the University of Dresden, where CSO Felix Lansing was a graduate student and later a postdoc. It originally started out nearly four years ago as RecTech, bankrolled by a €3.4 million grant from a German government initiative for life science startups, but officially launched as Seamless at the start of this year. At the helm is CEO Anne-Kristin Heninger, who was a scientific project manager for RecTech at its inception and has been in charge of the operations and the business side of the startup. Wellington Partners and Forbion are the venture capital backers behind the biotech. Part of Seamless’ seed funding also includes a new €3.8 million grant from the German government. For many years, recombinases have been a staple of basic science research used to study how genes are expressed, but now Seamless and others are leveraging them for future medicines. Prime Medicine, founded by the Broad Institute’s David Liu, is working on a technique called PASSIGE that uses a prime editor to put a target site where it wants in the DNA, so a recombinase can then swoop in and edit the gene. Stealth biotech Tome Biosciences, co-founded by MIT fellows Omar Abudayyeh and Jonathan Gootenberg, house PASTE, a technology that fuses the recombinase and the parts of a prime editor together. Seamless, on the other hand, is pointing the recombinases to their targets by altering the recombinases themselves. Seamless’ designer recombinases take time to make. “When I started in 2016 with my PhD, it took me one and a half years to create my first pair of designer recombinases,” Lansing said. “But then, ramping up the technology and understanding it, we are now down to a couple of months for making a new enzyme.” “We really had emphasis put on speeding up the process of generating [new recombinases] because that will truly unlock the usage in a broader aspect and because we would like to test many things that are very versatile,” he added. Seamless is still in its early stages, and Heninger said that next steps will be to mature the platform and build out Seamless’ pipeline. She said it was too early to put a timeline on milestones for the company, like when it would be in the clinic. First, the biotech is likely to work on ex vivo approaches as it looks into potential delivery technologies for in vivo therapies, Lansing said. On delivery, Heninger added that the biotech may look for potential collaborators. Delivering gene editors poses a major limiting factor for what therapies can be made successfully, giving rise to a new slate of biotech companies focusing specifically on just that, including Feng Zhang’s Aera Therapeutics , which launched last month. Liu and Keith Joung are the scientific founders behind another delivery biotech called Nvelop Therapeutics. When asked how Seamless’ platform compared to other gene editing tools, Heninger said, “It’s important to point out to maybe not compare the technologies. Rather say, what can we address best with our technology? And they have good indications they can address with their technologies. I would rather think about it that way.”
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