We often imagine DNA as a stringlike molecule that’s easily scrunched up. But our six-foot-long genomes only fit inside our cells thanks to an intricate spooling system. Left on its own, DNA’s famed double helix is actually quite rigid and rather difficult to stuff inside the tiny lipid nanoparticles favored by gene editing companies for delivering genetic medicines.
Kano Therapeutics, a new spinout of MIT, believes the answer to the packaging problem could be as simple as using floppier single-stranded DNA in place of the natural double-stranded molecules.
To put that idea to the test, the Cambridge, MA-based startup raised $7.15 million in seed funding and secured an early-stage partnership with Novo Nordisk, its CEO and co-founder Floris Engelhardt exclusively told Endpoints News.
“Single-stranded DNA is fifty times more flexible than double-stranded DNA and results in healthier edited cells because the innate immune system doesn’t get triggered as much,” Engelhardt said. “So it’s just inherently a better DNA payload.”
It seems like an obvious solution, yet single-stranded DNA is notoriously tricky to work with and expensive to make, especially in the compact circular form well-suited for cell and gene therapies. Although making the DNA at scale is a big part of Kano’s mission, Engelhardt said she isn’t trying to compete with other gene synthesis companies.
Instead, Kano is focused on the red-hot field of gene insertion therapies that aims to add or replace entire genes to treat inherited diseases or create supercharged cell therapies to fight cancer and autoimmune conditions.
Numerous startups dedicated to gene insertion have launched over the past year, and several high-profile academic labs have revealed new methods for uploading large chunks of DNA into cells. But Engelhardt wouldn’t name specific diseases or specific gene editing technologies that the company is working on.
Uli Stilz, head of Novo Nordisk’s Bio Innovation Hub, said in a statement that the company began working with Kano in January because it thinks single-stranded DNA will have advantages “on crucial parameters, like integration efficiency, cellular toxicity and editing accuracy.”
“We’re excited about the approach that Kano is pursuing, and think that our collaborative efforts, if successful, have the potential to unlock first-in-class non-viral genetic therapies for chronic conditions,” he added.
Engelhardt earned a doctorate at the University of Munich working in the field of DNA origami, which combines physics and artistry to morph the genetic molecules — often in their single-stranded form — into bewildering shapes. That experience got her recruited to a postdoc at MIT in 2020.
In the lab, she learned that the genetic molecule’s natural tendency to base pair with itself can be helpful in some instances and a hindrance in others. At Kano, her team is refining the rules for designing DNA strands that work as well as possible.
It’s a different approach from that of most gene editing companies, which often focus on the enzymes responsible for altering DNA, or the nanoparticles used to get them into cells. But Engelhardt thinks that there’s room to improve the payload, too.
“You cannot stick to the standard old plasmid DNA just because it’s cheap,” she said. “You need to adapt the payload to the delivery, as much as you are innovating the delivery.”
Kano’s seed funding was co-led by The Engine Ventures, a tech-focused investor with ties to MIT, and Vsquared Ventures, a European Union-backed investor in Germany.