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, called 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.
The original Human Genome Project, which mapped the entire genome, began in 1989, and a ‘rough cut’ version of the results was completed by 2000.
But scientists need not only a greater understanding of DNA, they also need faster and cheaper methods to conduct that research.
The team at Oxford Nanopore Technology, now based at Oxford Science Park, continues to develop their nanopore technology for DNA sequencing. 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.
A lipid bi-layer surrounds the nanopores to give total electrical insulation. Electrodes at the 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 readout of the base’s identity.
Their nanopore platform technology, still being refined, is called GridION.
Chief executive Dr Gordon Sanghera said: “It’s a bit like having IT servers. For a small research outfit, you can have just one, but each ‘node’ as we call it can be stacked to create a really powerful array.
And the beauty of it is it works in real time. You do not have to spend days making DNA copies, adding marker tags or spend a small fortune on a camera that reads fluorescence.”
The GridION is programmable to the researcher’s needs, starting with a quick yes/no readout on the presence of a disease or condition, then drilling down to give finely detailed analysis of the sample.
The company is pursuing two methods of DNA analysis and measurement. One looks at strands of DNA, while the other examines individual nucleotides, strands cut into pieces by a naturally occurring enzyme called exonuclease.
Taking accurate readings from strands involves slowing them down as they pass through the nanopore.
Pioneering research by the University of Santa Cruz, one of Oxford Nanopore’s partners, builds DNA on each strand as it passes through the tiny orifice, so slowing it down.
In 2009, the company extended its operations into protein research. Proteins are the output from the genome, and the work is a natural progression from existing studies.
Dr Sanghera said: “Our GridION platform is easily adapted to measure proteins rather than DNA. Our systems offer a doorway into cells.”
More and more, scientists are coming to realise that understanding proteins and their up and down regulation in diseases is even more important than DNA.
Oxford Nanopore’s business is far removed from the traditional small biotech approach. The team looks at the bigger picture, aiming for global impact, not quick wins.
Marketing of the company’s products is handled by US giant Illumina, which is capitalised at between £4 and £6bn. Illumina is also a shareholder.
Licensing deals and collaborations have been established with the five major nanopore academic research centres, including Oxford, Santa Cruz and Boston.
Funding is a mix of the UK and US, but with no traditional venture capital. Rather, these are institutional funds that encourage Oxford Nanopore in their ‘big picture’ model.
“We find the Americans in particular are geared to this approach,” Dr Sanghera said.
In line with this, funding rounds have been substantial. In early 2009, £17.4m was raised and a recent injection has brought in £25m.
Staff has increased from 25 in 2008, to 95 in 2011. They include microbiologists, electronic engineers, electrophysiologists, mathematicians and software specialists of 18 or 19 different nationalities.
Not only are these people some of the best in the business, it is essential that each one must be able and prepared to consider and offer opinion on subjects outside their own specialism. This results in a synergy key to driving the company forward.
Dr Sanghera said: “In that way, we’re like a Formula One team. And, just like an F1 team, we’re out for substantial wins.”
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