Ambitious unicorn hopes to improve DNA analysis

gENETICISTS LIKE compare the progress of their field with the breakneck speed of IT innovation. There, the big, slow computers evolved into the fast mid-size desktops, and then into the handheld supercomputers known as smartphones. Likewise, the sequencing of the first human genome was announced with great fanfare in 2003. It took 13 years and cost around $ 3 billion. Two decades later, sequencing a human genome will cost you around $ 600 and could be done in a week.

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Gordon Sanghera, boss of Oxford Nanopore, a company based in the eponymous UK university town, believes there is room for more, however. As The Economist went to press, his company was about to debut on the London Stock Exchange. Its technology, nanopore sequencing, can reduce the cost of genetic analysis and reduce the time required from days to hours or even minutes. At the same time, just like smartphones have done with computing, it can make gene sequencers small enough to fit in a pocket rather than on a desk.

Nanopore sequencing uses modified versions of proteins that in nature open holes in cell membranes to allow ions (electrically charged atoms of things like potassium and chlorine) to enter and exit. These proteins are used to punch holes in a membrane separating two chambers full of liquid, and an electric current is applied. The DNA to be sequenced is then introduced through the hole (see diagram). DNA stores its information using four different chemical bases, abbreviated as A, VS, g and T. Each has a different shape and partially blocks the pore in a different way. This causes different fluctuations in the current, allowing the sequence of bases to be read.

The idea of ​​sequencing nanopores dates back to the 1990s, says Dr Sanghera. But its commercialization took many years. One trick is to make sure DNA molecules move through pores at a predictable rate and never turn back, which the company solved with a specially designed molecular ratchet. The integration of the biological elements of the technology with those of silicon has been difficult. And a pore by itself does not perceive individual bases, but combinations of them. The translation of these signals is done using machine learning, a technology that has only taken off in recent years.

Nanopore sequencing offers several advantages over other approaches. Its compactness is one of them. Oxford Nanopore’s smallest product, the MIDmION, is the size of a large cell phone. Existing sequencers look like fridge-freezers or (at best) microwave ovens. The MIDmIONThe thoroughness of the s enables field analyzes without the need to send samples to a remote laboratory. It has been used everywhere, from Norwegian glaciers to Welsh coal mines to the International Space Station.

Another advantage is speed. Previous technologies have cut DNA into fragments, made copies and labeled them with fluorescent chemicals. That takes time. The record for sequencing a whole human genome is estimated at 13 hours. Oxford Nanopore estimates that it can reduce that steadily to a handful of hours. And the nanopore approach also provides continuous reading. Other methods only give a result at the end.

Chop DNA in tiny fragments, meanwhile, makes it difficult to understand what is happening in regions made up of repeating sequences. Nanopore-based devices can read pieces of DNA millions of bases long, providing a clearer picture of what’s going on. And they can detect methylation, a chemical change in bases that is an important way in which gene expression is regulated in a body.

Launch sequence

On paper, the sequencing of nanopores seems transformative. Whether this will actually happen remains to be seen. Like all good tech startups, Oxford Nanopore has yet to turn a profit, although it hopes to do so within five years. (His losses last year were £ 73million, or $ 98million, on earnings of £ 114million.) Julian Roberts, an analyst at Jefferies, a bank, says the global market for sequencing genes are worth maybe 7.5 billion dollars a year and growing “in low teens [per cent] per year – healthy, but not spectacular ”. It is dominated by Illumina, a San Diego-based company.

But, says Roberts, like computers, better technology can create new uses, making the market bigger. Cheap, real-time gene sequencing could improve everything from cancer treatment (researchers in Norway are looking to use it to read brain tumor genomes during surgery) to environmental modeling to disease surveillance (l (The usefulness of sequencing in the covid-19 pandemic has brought this application, in particular, to the fore in the minds of many epidemiologists).

The company’s choice to list in London rather than America flies in the face of conventional wisdom, that America offers smarter investors who are more willing to tolerate losses today in the prospect. a big win tomorrow. And he hopes, for now, to remain British. Its shareholder structure gives Dr Sanghera (or, if not available, two other senior executives) the ability to block unwanted takeovers. Mr. Roberts cites the example of Solexa, a British company acquired by Illumina in 2006 for $ 600 million. Today, Solexa’s technology is the basis of Ilumina’s business, and the American company is worth $ 64 billion.

This article appeared in the Science & Technology section of the print edition under the title “Un trou en un?”

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