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Sequencing 454 Abandons Stealth, Unveils Technology at GSAC

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Two years of industry buzzing paid off as Michael Weiner, vice president of molecular sciences at CuraGen subsidiary 454, spoke at a GSAC panel entitled “The Future of Sequencing: Advancing Toward the $1,000 Genome.”

Despite the panel name, president and CEO Richard Begley wants to make sure no one’s expecting too much: “I don’t want to mislead anybody that we’re going to run out the door and you’re going to be able to sequence the human genome for $1,000,” he warns.

That said, Begley obviously believes his company is more than a match for competitors in the field. He joined 454, which was spun out of CuraGen in 2000 with just six or seven people and ramped up in the second half of 2001, this January from his previous post at Agilent Technologies.

The 454 technology lured him because “it was a novel approach to dealing with genomic and proteomic measurement, but it wasn’t outlandish or very far off in the future.” The main idea is to miniaturize and massively parallelize genomic processes as much as possible.

The first technology to come out of 454, now at nearly 70 people, is an as-yet unnamed microbial sequencer. “We’ve sequenced an adenovirus in a couple of hours on this machine and reassembled it,” Begley says. “It’s the first test that [shows] this massively parallel approach works.”

The instrument dissects DNA into small fragments and sequences each fragment in parallel in several thousand to several hundred thousand 75 pico-liter wells, and the data is reassembled simultaneously. The platform combines sequencing and genotyping.

It’s a very different method from capillary electrophoresis or gel plate sequencing, Begley said. It also differs from the current frenzy for single-molecule detection methods that have been hyped as the solution to inexpensive genome sequencing. “We do amplify the fragments to be sure that we have enough to do accurate sequencing,” Begley said.

In the next few months, 454 expects to release its first peer-reviewed technical papers fully explaining the technology. “We don’t advertise very much and you don’t hear about us very much,” Begley says.

With the release of the papers, 454 expects to emerge from stealth mode. Meantime, company scientists will be working on scaling up the technology to run millions of wells at a time, which would in theory enable large-genome sequencing. The platform will also be the base for many other applications. “We’ll definitely be looking at proteomics as time goes on,” Begley says. He foresees long-term use to improve drug discovery, facilitate genetic patient screening for clinical trials, and identify or detect pathogens.

— Meredith Salisbury

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