From molecular pore to global sequencing technology

The ability to read DNA and RNA quickly can help researchers understand disease, identify pathogens and investigate the genetic information that shapes living things. 

Nanopore sequencing offers a distinctive way to do this: reading individual strands of DNA or RNA directly and producing results in real time.

At UCL, Professor Stefan Howorka, Department of Chemistry, co-developed CsgG nanopore technology with Prof Han Remaut's lab at Vlaams Instituut voor Biotechnologie; this was subsequently licensed to Oxford Nanopore Technologies (ONT) and incorporated into its sequencing technology. 

The journey from university research to commercial application shows how finding the right route to market can help an innovation go further… 

What is a nanopore? 

Nanopores – as the name suggests – are pores that are just a nanometre wide. Some nanopores are proteins that form channels in biological membranes, while others can be manufactured in materials such as silicon or graphene. 

For DNA and RNA sequencing, nanopores can work as single-molecule detectors. Put simply, they help us to ‘read’ the genetic information contained within an individual molecule as it passes through the nanopore and an electrical current. Software can then measure and interpret these changes to determine the genetic sequence.

Problem to be solved

Some sequencing approaches can struggle to resolve long or structurally complex regions of DNA. Other applications for DNA/RNA sequencing also require results more quickly and outside of a conventional laboratory setting.

Solution

Nanopore sequencing provides a different approach: individual, long molecules can be read directly as they pass through the pore, with genetic sequence data generated in real time. 

CsgG has characteristics that make it particularly well suited to nanopore sequencing. Its molecular structure enables individual DNA or RNA molecules to pass through the pore while changes in electrical current are measured and decoded.

This supports long-read analysis, real-time results and portable sequencing, enabling genetic material to be analysed in a wide range of settings.

This real-time capability has been particularly valuable in infectious-disease surveillance, helping researchers track emerging pathogens and inform public-health responses.

This combination meant nanopore sequencing was used to determine 50% of SARS-CoV-2 genomes in Africa, and 25% globally. 

How did licensing CsgG help Oxford Nanopore Technologies? 

Licensing CsgG nanopore technology in 2016 gave ONT a pore with stable electrical signals that could improve sequencing speed and accuracy and help strengthen the performance of the company’s commercial platforms. 

ONT had already spent around a decade developing the wider technologies needed for DNA nanopore sequencing, including miniaturising sequencing reactions within portable devices capable of running thousands of sequencing reactions in parallel. CsgG could therefore be incorporated into an established sequencing platform and developed as part of ONT’s wider technology.

ONT has since incorporated CsgG into a range of its commercial products, including the portable MinION sequencing device, which has also been used aboard the International Space Station.

How did UCL Ventures help with this licensing project? 

UCL Ventures worked with Prof Howorka to assess the technology, its potential applications, and the wider market before identifying licensing as the appropriate route. 

Early patent filing helped secure a priority date for the intellectual property, while UCL Ventures supported the necessary IP arrangements before the technology was licensed to ONT.

Generally, licensing suits focused technologies with clear applications, particularly where they can fit within an existing company's product roadmap. In this case, licensing CsgG meant the nanopore technology could be developed by ONT, which already had the technology and infrastructure. This allowed Prof Howorka to remain focused on his research.

The academic experience 

Professor Howorka said: “I truly enjoyed seeing the journey from scientific innovation over licensing to technology development, product innovation, and societal impact.”