Scarcely a day passes without some reference to DNA in the media, be it for criminal detection, or as a path to improved healthcare. Deoxyribonucleic acid (DNA) is a molecule that contains the instructions for the development and operation of living organisms. Each organism has one complete DNA code, known as a genome, and a copy of this genome is found in that organism’s cells.
DNA is a polymer of individual units known as nucleotides or ‘bases’. These are arranged in a ‘double helix’ structure like a twisted ladder. There are four nucleotides: Cytosine, Adenine, Guanine and Thymine, often written as C, A, G and T.
Every organism’s code is unique. Working out the order in which the bases are joined together in that code, gene sequencing, is the key to opening any number of doors that will benefit mankind.
Drugs research looks at the code — the genotype — and the phenotype, the way that manifests itself in a disease like diabetes. In turn, this leads to the development of personalised medicines, understanding which drugs will be effective on which patients and at what stage of the disease.
In public health, there is currently a study of the five different types of malaria and their drug resistance.
The recent case in the USA of anthrax being sent through the post resulted in two deaths. The culprit was identified through tracing the spores back to their original laboratory by their DNA.
These are but some examples of the powerful tools offered by DNA structures.
The original Human Genome Project, which mapped the entire genome, cost $3bn (£1.74bn). Costs have gradually decreased through the millions down to between $100,000 and $400,000. But for cost effective research into relevant portions of the genome, the price has to drop to between $10,000 (£5,800) and $1,000 (£580). Hence, the $1,000 genome.
Presently, gene sequencing is costly. It uses fluorescent labelling of each base, which is photographed with a special and expensive camera to determine the label’s colour. That colour identifies the base.
The fluorescence is weak, so needs amplifying, which in turn leads to errors. The reagents, and the skilled team needed to run and interpret sequences, all add to the costs.
Oxford Nanopore Technologies is developing an accurate and cost-effective system giving a direct read-out of the base’s identity. A nanopore is a tiny protein excreted by bugs and resembles a mushroom with a thick head. A minute hole runs through each head and stem.
The nanopores are placed in wells — holes the size of human hairs — in a silicon chip. What is called a lipid bi-layer surrounds the nanopores to give total electrical insulation.
Electrodes at top and bottom pass a minute current through the nanopores.
The DNA strands are passed through the holes, molecule by molecule. Each molecule or base has a different shape and that shape affects the current, which is translated into a direct read-out of the base’s identity.
Chief executive Dr Gordon Sanghera said: “For once we are having to slow nature down. Left to their own devices, the molecules would rush through the nanopores far too fast for accurate readings.
“So we use a natural enzyme that traps each molecule as it enters the nanopore. That lets us measure one base at a time.”
Dr Sanghera and his rapidly growing team are scaling up the chips with an eventual target of hundreds or thousands of wells per chip. Using their expertise and commercially-available technology, their goal is an affordable and highly-accurate platform which can be sold for research into any DNA sequence.
Nanopores will be replaced with solid-state wells given time, but creating identical wells using ion beams to drill the chips has yet to be perfected.
Spun out from Oxford University in 2005 by founder Professor Hagan Bayley, first round funding in 2006 raised £7.5m.
Company numbers have leapt from under 30 to 45, since a second round of funding in March raised £10m to fund substantial growth. A heavy recruitment programme is ongoing to complement the biologists, chemists, electronics, fluidics and instrumentation engineers at the company’s Begbroke base.
In June, the company brought in two heavyweights, Dr John Milton and Clive Brown, both with exceptional track records in sequencing. Space is at a premium, with Oxford Nanopore occupying one building at Begbroke and much of the Centre for Innovation and Enterprise. With a portfolio of between 75 and 85 patents, the company has a robust intellectual property library. Its backers are a mix of institutional investors and private individuals, many with Oxford connections.
Professor Bayley’s network across major universities including Harvard, California, MIT and Texas means collaborations that assist with development of the technology. Director of communications Zoe McDougall said: “This is hot space. One of our rivals in the US has just raised $100m in venture capital, one of the biggest VC deals ever.
“The possibilities for our growth are huge.”
Name: Oxford Nanopore Technologies Established: 2005 Chief executive: Dr Gordon Sanghera Number of staff: 45 Annual turnover: Confidential Contact: 0870 4861966 Website: www.nanoporetech.com
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