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The Guardian - UK
The Guardian - UK
Business
Julia Kollewe

Small wonder: big DNA advances loom at university startup Oxford Nanopore

Dr Gordon Sanghera, CEO, shows off the small Oxford Nanopore DNA/RNA sequencing device.
Dr Gordon Sanghera, CEO, shows off the small Oxford Nanopore DNA/RNA sequencing device. Photograph: Graeme Robertson/The Guardian

Not far from Didcot, once a halfway stop between London and Bristol on the Great Western Railway celebrated for Isambard Kingdom Brunel’s engineering, innovation has returned with a hi-tech factory manufacturing DNA and RNA sequencing machines.

Oxford Nanopore, a spinout from Oxford University, produces devices used to identify viruses and spot variants in the genetic makeup of humans, animals and plants. Its sequencers have been used to track Covid-19 variants globally and are now being trialled on intensive care patients with respiratory infections at Guy’s and St Thomas’ hospitals in London, and in the fight against the 200 drug-resistant strains of tuberculosis, the second-biggest killer worldwide after Covid in 2020.

“Our DNA is not static: from birth to the life cycle of a plant, or an animal or a human, it changes over time, due to lifestyle, environmental factors,” says Gordon Sanghera, Nanopore’s co-founder and chief executive. “We are entering the genomic era; genomics will be at the centre of everything.”

Demand from academics, governments and businesses is growing. Sanghera plans to build another factory in the next few years – probably in the UK, although he won’t rule out Asia or the US. “The plan is to be a global tech player,” he says.

Founded in 2005 by three scientists who met at Oxford University, the company grew out of research by Hagan Bayley, one of the trio, who is still a professor of chemical biology there. In traditional sequencing, DNA samples are chopped into smaller pieces and copied, which can introduce errors. Bayley researched how a tiny hole, or nanopore, in a protein can be used to identify the molecules in DNA that pass through it, in a process compared by Sanghera to “sucking spaghetti really fast”.

Nanopore’s factory on the Harwell campus near Didcot was built within 12 months in 2018. This is where flow cells are made, a key component of the sequencers, which have to be replaced regularly, much like printer cartridges.

Nanopore’s operations chief, Rhodri Davies, explains how they work: “A nanopore is inserted within a membrane and a current passes through it. On either side there is an ionic solution and a couple of electrodes. As DNA passes through the hole, it modulates that ion flow – a bit like turning a tap on or off. These different levels of current are signals and our smart electronics convert that into the alphabet of DNA.”

On our tour of the factory, we see a large room with orange lighting similar to a darkroom where P-chips – product chips with a sensor, “the heart of the system” – are manufactured from wafers. In the room opposite, Nanopore staff are busy assembling flow cells using the P-chips. The firm intends to automate the assembly process soon. The sequencing machines are largely made in the UK, across the different Oxford sites.

The technology can be widely used to track disease outbreaks, optimise crop growing and protect endangered species. For example, Lara Urban, a Humboldt research fellow at the University of Otago in New Zealand, uses a handheld Nanopore device in the jungle to support conservation of the critically endangered kākāpō parrot.

Nanopore floated on the London Stock Exchange just over a year ago in one of the UK’s best-ever market debuts. The shares jumped 44%, valuing the firm at nearly £5bn, and turning Sanghera and the other founders into paper millionaires. The share price has since plummeted, similar to peers on Nasdaq including California rival Illumina, which dominates the global sequencing market. Nanopore shares are now worth 279p, compared with its listing price of 425p.

Sanghera says this reflects the worsening economic climate, adding that if Nanopore had not issued limited anti-takeover shares to him and two other executives, allowing them to block hostile approaches, the company would be “a sitting duck” for a takeover.

Many promising UK science and tech startups on the brink of commercialisation have been acquired by bigger overseas rivals over the years. Medisense, the glucose monitoring startup, another Oxford spinout where Sanghera started his business career, was sold to US firm Abbott in 1996, he recalls, while Illumina in 2007 snapped up Solexa, a Cambridge university spinout whose technology forms the basis of its sequencing instruments. “We’ve just got to stop this happening,” Sanghera says.

Referring to the Covid jab developed by Oxford University and AstraZeneca, Sanghera adds: “[It] made us [Britain] think about how we need to do things ourselves.”

The anti-takeover shares expire in two years, but if Nanopore carries on growing on the current trajectory, “we expect to be in a strong position”.

Nanopore received a one-off sales boost of £52m from Covid test kits in the six months to 30 June, but also made £71m from its other devices, up more than a third from a year earlier. It expects to generate revenues of between £145m and £160m this year.

The wider British life sciences sector is sluggish, however. Revenues from UK companies making life science products declined by £7.7bn in real terms, adjusted for inflation, between 2011 and 2020, according to government data.

Sanghera served on the council of business leaders under Theresa May and Boris Johnson and says that there was a real will at a senior level in the government to make the UK a “life sciences superpower” and to try to create hi-tech jobs. “It’s just cascading that down to the tech companies that could do with some streamlining,” he says.

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