An outfit founded in 2005 in Oxfordshire has raised £74 million in investment, is hiring at a time when many companies are letting people go - but still has no product or service for sale.
Oxford Nanopore Technologies, a spin-off from the University of Oxford, is quietly developing an intriguing new way to analyse DNA. It’s a technique that could revolutionise doctors’ use of genetic data and could become the future of healthcare at a time when the British government is expecting the NHS to be “working hand-in-glove with industry as the fastest adopter of new ideas in the world”.
Oxford Nanopore is betting all its money and expertise on an electronic technology for gene sequencing. One conventional technique includes dying different sections of the DNA distinct colours so that machines can ‘read’ the DNA.
Nanopore sequencing brings sophisticated electronics into the equation, in a bid to accelerate the process, which currently takes several weeks. Rather than ‘looking’ at every section of the DNA, nanopore technology uses electronic sensing. An electrical current is fed through very small holes (‘nanopores’) in a membrane and then the DNA sample is passed through this hole. Since each pearl of information along the string of a DNA molecule has a certain shape and size, each disrupts the electrical signal in a characteristic way, allowing the machine to infer its type.
Oxford Nanopore’s approach is grounded on its proprietary GridION hardware. Within that, the company has developed two types of sensor microchip: one that can process information from multiple nanopores at the same time, and one that translates the signals from the nanopores into useful bytes that can be interpreted by machines and humans.
All a numbers game
The reason DNA sequencing is so complex is because of the numbers involved. A person’s DNA contains around 3.2 billion chemical bases, divided between 23 chromosomes. Studying someone’s DNA has to begin with understanding the order of these bases.
“Because the bases are structurally different, they create characteristic disruptions in a current as they pass through a nanopore,” explains Gordon Sanghera, Oxford Nanopore’s chief executive. “So their order can be determined using nanopores. Analysing one DNA molecule at a time using one nanopore doesn’t yield enough data for most researchers - we have to scale it up.” That’s where the company’s special microchips come in: they can perform millions of calculations at once.
On exactly how they do that, Sanghera is holding his cards close to his chest. DNA sequencing is a fiercely competitive field. But soon the major industry players will need to unveil their technologies if they are to compete in the recently announced Archon Genomics X Prize, a competition that aims to find a technique that can provide a medical-grade human genome within 30 days for $1,000. An Oxford Nanopore spokesperson said that she did not want to comment on whether the company would compete, although it is known to be interested in throwing its hat into the ring.
Competitive pressure may force the company to enter this high-profile contest. One of the stalwarts of the sequencing market, the US company 454 Life Sciences, is confident that the target cost can be easily met. “We will closely evaluate our participation in the coming years as we develop and bring to market third- and fourth-generation instruments with the capacity to rapidly decode an individual’s complete genome for well below $1,000,” says Thomas Schinecker, 454’s president.
The catch for Sanghera and co is that 454 is developing nanopore sequencing technology in partnership with the brains at IBM. The tech giant entered this field when computational biologist Gustavo Stolovitzky bumped into engineer Stas Polonsky in a corridor at the IBM research centre just outside of New York one day. Marrying biology and electronics, the pair set about building a better gene sequencer. They eventually created the DNA Transistor. According to Polonsky, the machine is derived from IBM’s bread and butter. “It is made by the same materials we use to build microprocessors, so it’s not that far a jump,” he says.
“Not years away”
Last year, IBM and 454 joined forces to develop the technology. According to Schinecker, while other nanopore sequencing technologies use a protein-based nanopore, the IBM DNA Transistor uses a synthetic silicon membrane. “We believe this approach offers significant advantages in terms of control, robustness, scalability and manufacturability,” Schinecker said.
Schinecker’s final four words constitute the holy grail of any new technology. As Henry Ford knew, there is little point in making a better car if you can’t build millions of models. With that in mind, 454 recently licensed some new technologies from Arizona State University and Columbia University in order to develop its collaboration with IBM. Polonsky notes that a new technology will still take years to reach the market. “If we are lucky, we would see some working stuff in five years,” he predicts. “But if not lucky, decades, maybe more.”
Just what the doctor ordered
Early adopters of the new nanopore technology will no doubt be looking for three things. “We always talk about cheaper, faster, better,” says Dr Harold Swerdlow, head of sequencing technology at the Wellcome Trust Sanger Institute. Specific to DNA sequencing, Swerdlow says, that translates into “a platform that could generate data faster or cheaper or [with a] longer read length.”
“Read length” refers to the amount of continuous DNA analysed: essentially, how long each section of DNA is. The longer the read length, the better, since shorter lengths have to be cobbled together by the computer, which introduces uncertainty. At present, many technologies are limited to read lengths of 35 to 150 base pairs. “The unique advantage of 454 sequencing is the high-quality, long reads,” boasts Schinecker, “from 400 base pairs up to 750-plus base pairs in length.”
Nanopore sequencing, even in its trial stages, is smashing the fastest time available in the industry at the moment. At Oxford Nanopore, Sanghera would not say the target read length of his new system, just that it is “very long”. The company is also tight-lipped on when it might launch its potentially disruptive technology. A source confirmed only that Oxford Nanopore “is not years away” from releasing its gizmo.
The company recently posted adverts for four customer-facing jobs. These include a vice president of sales and marketing and a vice president for manufacturing. The ad for the latter job reads: “The role will drive the expansion from existing internal and external pilot manufacturing capabilities, scaling through a high-growth phase to commercial launch of the GridION system.”
An electronic future
A cross section of the DNA Transistor, with a single-stranded DNA molecule moving in the midst of (invisible) water molecules through the nanopore
That is the kind of language the British government is keen on. This week, the prime minister announced a £180m “catalyst fund” to help biomedical start-ups develop new technologies that benefit healthcare. Although this specific fund is for drugs, it shows that money tends to flow towards the life sciences.
Betting hard cash on the notion that the future of DNA sequencing lies in electronics may not be a bad idea. Polonsky has expected the marriage since he heard a colleague remark in the 1990s that the future of semiconductors lay in applying them to other fields. “If you want high-margin business, the next thing is hybridisation,” says Polonsky. “And you can hybridise semi-conductors with bioscience.”
Indeed, powerful consumer electronics companies Intel and Samsung are also rumoured to be looking at DNA sequencing. The new technology race is on, and it’s biological.