A bit strange: major DNA advances loom at university startup Oxford Nanopore

NNot far from Didcot, once a halfway stop between London and Bristol on the Great Western Railway celebrated for the engineering of Isambard Kingdom Brunel, innovation has returned with a high-tech factory that manufactures DNA and RNA sequencing machines.

Oxford Nanopore, a spinout from Oxford University, produces devices used to identify viruses and detect 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 tested 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 in the world after Covid 2020 .

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

Demand from academics, governments and companies 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 technology player,” he says.

The company was founded in 2005 by three scientists who met at Oxford University and 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 cut into smaller pieces and copied, which can lead to errors. Bayley investigated how a tiny hole, or nanopore, in a protein can be used to identify the molecules of DNA passing through it, in a process that Sanghera compared to “sucking spaghetti really fast”.

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

Nanopore’s operations manager, Rhodri Davies, explains how they work: “A nanopore is inserted into a membrane and a current passes through it. On each side there is an ion solution and a pair of electrodes. As the DNA passes through the hole, it modulates the ion flow – a bit like turning a faucet 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 that resembles a darkroom where P-chips – product chips with sensors, the “heart of the system” – are made from wafers. In the room opposite, Nanopore’s staff are busy assembling flow cells using P-chips. The company intends to automate the assembly process shortly. The sequencing machines are largely manufactured in the UK, across the various Oxford sites.

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

Nanopore was listed on the London Stock Exchange just over a year ago in one of the UK’s best market debuts ever. Shares rose 44%, valuing the company at almost £5 billion and making Sanghera and the other founders paper millionaires. The share price has since plummeted, along with rivals on the Nasdaq including California rival Illumina, which dominates the global sequencing market. Nanopore shares are now worth 279p, compared to the stock price of 425p.

Sanghera says this reflects the deteriorating economic climate, adding that if Nanopore hadn’t issued buyout restricted stock to him and two other executives, enabling them to block hostile approaches, the company would be “a sitting duck” for a take-over.

Many promising UK science and technology startups on the brink of commercialization have been acquired by larger foreign rivals over the years. Medisense, the glucose monitoring startup, another Oxford spinout where Sanghera started his business career, was sold to the American company Abbott in 1996, he recalls, while in 2007 Illumina bought up Solexa, a Cambridge University spinout whose technology forms the basis of its sequencing instruments. “We just have to stop this,” says Sanghera.

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

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

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

However, the wider UK life sciences sector is sluggish. Revenues from UK companies making life science products fell by £7.7 billion in real terms, adjusted for inflation, between 2011 and 2020, according to government data.

Sanghera sat on the Council of Business Leaders under Theresa May and Boris Johnson and says there was a real desire at senior levels in government to make the UK a “life science superpower” and to try to create high-tech jobs. “It’s just bringing it down to the technology companies that could make some efficiencies,” he says.

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