Harnessing single-stranded DNA for precision genome editing.
The future of medicine depends upon expanding our ability to alter human genetic code. But despite the astonishing progress of the last decade, actually inserting genetic information into the genome for therapeutic purposes remains an unmet challenge. If pharmaceutical companies are to broaden their drug portfolios to address complex diseases, they need new tools—unencumbered by today’s limits on complexity and scalability. “If you want to insert a gene-length piece of genetic material, all of the methods to do that today are problematic,” says Floris Engelhardt, co-founder, CEO, and CSO of Kano Therapeutics.
Kano, a biotechnology startup with roots in the Bathe BioNanoLab at MIT’s Laboratory for Nucleic Acid Nanotechnology, is meeting that challenge by pioneering single-stranded DNA as a safe, efficient, and flexible biomaterial for gene insertions. Unlike the current state-of-the-art techniques, which typically rely on double-stranded DNA or viral vectors, Kano Therapeutics’ successful harnessing of single-stranded DNA offers a transformational alternative: a superior new platform for the delivery of genetic information to a cell. Kano’s ability to design and manufacture ssDNA gene vectors at scale creates a new category of material for the biotech ecosystem. “Our biomolecules are not simply raw material anymore, but functional drug components,” Engelhardt says.
Kano’s proprietary technology emerged out of the Bathe BioNanoLab’s early success at engineering DNA nanostructures for a diverse set of uses—including data storage, quantum computing, and vaccine delivery. When pharmaceutical companies became aware of the Bathe lab’s approach to making longer ssDNA molecules in large quantities, they could see its potential for therapeutics. Their experts in genomic engineering already knew two key advantages of ssDNA: it is better suited to efficiently replace whole genes; and it is safer, because it is less likely to trigger the innate immune system. What was missing was the ability to produce custom gene-length strands with suitable precision, and at commercial scales. Existing ssDNA production methods required a letter-by-letter assembly that was error-prone beyond a couple hundred base pairs—grossly inadequate for the 1,000+ letters needed for gene-length molecules. But Kano’s core IP—based on Engelhardt’s expansion of the Bathe BioNanoLab’s techniques—breaks this manufacturing bottleneck. Its fermentation process makes nature the genetic proofreader, enabling the precision-manufacturing of ssDNA gene vectors in custom lengths and sequences, and at scales sufficient for commercial applications.
With this technology, Kano Therapeutics is staking an innovative position in the biopharmaceutical market. Single-stranded DNA has an unusual breadth of potential applications; it can work across therapeutic delivery technologies, disease indications, and cell types. Kano’s design and engineering platform can supply custom ssDNA molecules with properties specific to a broad range of needs—whether pharmaceutical companies heading towards clinical trials, or specialty producers engineering new tools for cell therapies. And it can manufacture those biomolecules at scale. “Companies working on gene editing medicines need the technologies that will make therapeutic gene insertions a reality,” says John Vroom, Kano’s head of operations and business development. “Our gene vectors can do that.”
The end result is a new category of tool for genetic medicine: a way to write complex information into a biomolecule that promises to expand the realm of therapeutics. “Current medicines can change a letter—or maybe a word—of genetic information,” says Engelhardt. “We are talking about replacing whole sentences—or even paragraphs—of instructions. And that has a huge impact.”