Kano Therapeutics Pioneers Circular DNA for Safer, More Effective Gene Therapies
A new approach using circular single-stranded DNA (cssDNA) promises to overcome limitations of traditional gene therapies, offering a less toxic and more efficient delivery method for treating a wide range of diseases.
The promise of gene therapy – correcting faulty genes to cure disease – has long been hampered by a critical challenge: the body’s immune response. To our immune system, potentially lifesaving gene therapies can resemble perilous infections. This is largely because conventional genetic medicine relies on viruses or double-stranded DNA to deliver genetic facts, triggering toxic immune stimulation and posing difficulties in packaging for cellular delivery. Kano Therapeutics, a biotechnology company spun out of MIT, is tackling this problem head-on with a novel platform based on circular single-stranded DNA (cssDNA).
Kano is developing gene-editing technologies utilizing cssDNA, a biomolecule demonstrably less toxic than its double-stranded counterpart and more stable than RNA. This innovative approach aims to deliver genetic material more efficiently to various parts of the body, opening new avenues for treating genetic diseases, cancers, and beyond. The company, founded by former MIT postdoc Floris Engelhardt, professor of biological engineering Mark Bathe, and john Vroom MBA ’22, has created a platform for manufacturing cssDNA of customized lengths and sequences.
“We can work with CRISPR and other gene-editing technologies,” explained Engelhardt. “CRISPR finds a location in a genome, binds to it, and cuts at that location. That allows you to edit a gene or stop a gene from functioning. But what if you have a loss-of-function disease where you need to insert a new piece of genetic code? Our approach allows you to replace whole genes or add genetic information.”
The foundation for Kano’s technology stems from research conducted in Bathe’s lab around 2019,which detailed methods for engineering the sequence and length of cssDNA molecules. These molecules, while previously used in laboratory settings, gained meaningful attention for their potential to improve gene therapies, quickly attracting interest from several pharmaceutical companies. According to Bathe, “Single-stranded DNA is a little like messenger RNA, which can code for any protein in any cell, tumor, or organ. it fundamentally encodes a protein, so it can be used across diseases, including rare diseases that may only affect a few people in the country.”
Engelhardt’s prior work as a ph.D. student in Munich further solidified her expertise in cssDNA. A chance encounter with Bathe at a conference led to a pivotal decision. “We were considering collaborating on research,” Engelhardt recalled. “Then Mark heard I was finishing my Ph.D. and said, ‘Wait a minute.Instead of collaborating, I should hire you.’ ” Within 48 hours of submitting her doctoral thesis, Engelhardt received an offer to join Bathe’s lab as a postdoc, drawn by the chance to focus on research with direct patient impact.
The founders quickly recognized the limitations of existing CRISPR-based treatments, including potential toxicity and inefficient delivery. They also noted that the immune system frequently enough labels CRISPR as foreign, limiting treatments to a single administration. Kano’s cssDNA platform addresses these challenges by offering a more biocompatible and versatile alternative.
To accelerate commercialization, Engelhardt leveraged MIT’s extensive entrepreneurial resources, including a “founder speed dating” event where she met Vroom, the Venture Mentoring Service, classes at the Sloan School of Management, and the Industrial Liaison Program. Bathe also advised her to engage with MIT’s Technology License Office from the outset.
A key innovation lies in Kano’s manufacturing process. The company utilizes fermentation to produce cssDNA, a more cost-effective approach compared to traditional chemical DNA synthesis. “No one had the ability to access this type of genetic material, and so a lot of our work was around creating the highest-quality, economically scalable process to allow circular single-stranded DNA to be commercially viable,” Engelhardt stated.
Since completing her postdoctoral work in 2021, Engelhardt and Vroom have been focused on securing funding and building the company.Kano’s current platform can accommodate genes up to 10,000 nucleotides in length. The company is actively pursuing partnerships with pharmaceutical companies to enhance the targeting and potency of their gene therapies. Such as, partners could leverage Kano’s platform to combine genes like CD19 and CD20, expressed in certain tumor cells, requiring both to bind before entering a cell’s genome and initiating edits.
Engelhardt emphasized the increased flexibility of Kano’s approach compared to CRISPR.”We realized working with pharmaceutical companies early on in my postdoc there was a lack of design understanding as of the lack of access to these molecules,” she said. “When it comes to gene or cell therapies, people just think of the gene itself, not the flanking sequences or anything else that goes around the gene. Now that the DNA isn’t stuck in a double helix all the time, I can create small, three-dimensional structures-think loops or hairpins-that work, for example, as a binding protein that pulls it into the nucleus. That unlocks a wholly new path for DNA because it makes it engineerable-not only on a structural level but also on a sequence level.”
To foster broader collaboration, Kano is implementing partnership agreements that prioritize access and widespread adoption over maximizing royalty percentages. A recent collaboration with Merck KGaA combined Kano’s cssDNA platform with the company’s lipid nanoparticle delivery solutions. Discussions are also underway with other major pharmaceutical companies to jointly advance cancer drugs into clinical trials over the next two years. “That’s exciting because we’ll be implementing our DNA into partners’ drug system, so when they file their new drug and dose their first patients, our DNA is going to be the therapeutic information carrier for efficacy,” Engelhardt explained. “As a first-time founder, this is where you want to go. We talk about patient impact all the time, and this is how we’re going to get it.”
Kano is also developing a comprehensive database mapping cssDNA designs to their activity, aiming to accelerate the growth of new treatments. “Right now, there is no understanding of how to design DNA for these therapies,” Engelhardt noted. “Everyone who wants to differentiate needs to come up with a new editing tool, a new delivery tool, and there’s no connecting company that can enable those areas of expertise. When partners come to us, we can say, ‘The gene sequence is all yours.’ But often its not just about the sequence. it’s also about the promoter or flanking sequence that allows you to insert your DNA into the genome, or that makes DNA package well into your delivery nanoparticle. At Kano, we’re building the best knowledgebase to use DNA material to treat diseases.”
ultimately, Kano Therapeutics envisions a future where cssDNA unlocks the full potential of gene therapy, offering safer, more effective, and more accessible treatments for a wide range of debilitating diseases.
