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With IP, New Enzyme, UK Nanotech Startup Readies for Action

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A UK-based Oxford University spinout is working hard to put itself on the map with a new kind of sequencing technology that represents the cutting edge in nanopore research. Launched in 2005, Oxford Nanopore Technologies is a next-gen sequencing upstart touting a label-free "nanolab-on-a-chip" that uses nanopores for single-molecule DNA sequencing.

The basis of the company's nanopore technology was provided by Oxford chemistry professor and company founder Hagan Bayley, who originally helped create a spinoff called Oxford Nanolabs using his research showing that a nanopore could differentiate between four nucleotide bases. And although Bayley's initial research made waves in the sequencing community, it was not quite ready for prime time deployment in commercial applications, says Zoe McDougall, director of communications at Oxford Nanopore Technologies. "So since that time, we've been internally developing [Bayley's] work and we now have a very advanced nanopore identification construct that has very high resolution, high identification of DNA bases," she says. "So the challenge with that is that the nanopore identifies one base at a time."

In May of this year, the company changed its name to Oxford Nanopore Technologies to help reflect its main mission of expanding possibilities for nanopore-driven technology. To this end, the young company wasted no time establishing licensing agreements to harness critical nanopore technology from institutes in the US, including Harvard, the University of California, Santa Cruz, Texas A&M University, the University of Massachusetts Medical School, and the National Institute of Standards and Technology. In early August, the company signed an IP agreement with Harvard allowing it access to more than 60 nanopore-related patents. Then later in the month, the UK startup secured an exclusive IP deal with researchers at UCSC. The agreement will continue development of the nanopore technology from the laboratories of David Deamer and Mark Akeson, pioneers in the science of nanopore-based DNA analysis. To date, Oxford Nanopore has raised roughly $35 million to grease the wheels of its myriad research efforts and partnerships.

The current prototype system is built on an array that utilizes protein-based nanopores to act as molecular checkpoints detecting individual bases of DNA as they are passed through the nanopore. Each base binds to a cyclodextrin adapter as it passes through the nanopore, creating a characteristic disturbance in current.  The current flow is measured by electrodes, in turn identifying each base. Research indicates that this nanotechnology is so sensitive that it could be used to detect ionic pollutants in drinking water, agents of bioterrorism, and many critical disease biomarkers.

The next step in the development process for Oxford Nanopore Technologies is to make sure that each base is introduced into the nanopore at the correct pace and with enough control that the bases are identified accurately and in the correct order as they flow through. "We're coupling the protein nanopore with another protein which will fit on top of the nanopore," McDougall says. "We are in the process of doing that now. It's really the chemistry on attaching the enzyme so that it essentially fires each DNA base through the nanopore at the right trajectory, so that's our main body of work here at the moment."

Ultimately, McDougall says that the company sees itself as the leader — not just on the bleeding edge of nanopore sequencing tech development, but for any applications areas where nanopore technology can play a role. "We really think that we've corralled the best scientists in nanopore technology; and while we're developing in the application of nanopore-driven sequencing, nanopore is capable of even more than that," she says. "We're driving for the leadership position in nanopore applications, so that means not only having the first and second generation of nanopore sequencing technology, but also a whole range of identification systems beyond that."

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