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454, Solexa Mark Milestones; John West Unmoved by ABI s New Sequencing Plan

HILTON HEAD, SC — With the leading next-generation sequencing companies making strides in their pursuit of the $100,000 genome, 454 Life Sciences and rival Solexa have made what they claim are important milestones.

In a presentation at the Genomes, Medicine and the Environment Conference, held here this week, 454 founder Jonathan Rothberg disclosed that his shop "is starting a number of collaborations" with undisclosed pharmaceutical companies to determine whether its newly launched sequencing technology could be used to identify drug-resistant strains of HIV. The CuraGen subsidiary also confirmed that it has placed instruments at the Wellcome Trust Sanger Institute and Washington University, adding to deployments at the Broad Institute and the DOE's Joint Genome Institute.

And Solexa, which plans to release its instrument by the end of the year, said it has used its Single-Molecule Array technology to sequence a human bacterial artificial chromosome — an "important milestone" that bolsters the company's belief that it will "be the first to deliver whole human genome sequencing at $100,000 per genome."

But 454's announcement, together with ABI's recent disclosure that it is developing next-generation instruments of its own (see BioCommerce Week 10/6/2005), were discounted by Solexa CEO John West, whose sequencing-by-synthesis platform aims to rival 454's and ABI's.

"Our focus has been, 'How do we get to the whole human genome?"

Asked at the conference whether Solexa's decision to make its BAC-sequencing announcement was spurred by ABI's disclosure of its own R&D plans, West told BCW's sister publication GenomeWeb Daily News that "it wasn't lost on anyone [at the conference] that ABI didn't ... present" at the meeting.

ABI did sponsor a luncheon symposium at the meeting on Monday, during which users of its sequencing technology "share[d] their experiences, techniques and methodologies." However, the company had no plenary presentation during the conference.

West, who used to run ABI's sequencing business before joining Solexa, said it's a "very capable" business, but said "it's just hard to know what they're doing" with new sequencing technologies.

That 454 is talking with drug makers on what are essentially molecular diagnostics applications is noteworthy because Roche, 454's marketing and commercialization partner, has allied itself with the company because it was able to obtain the option to use its platform if and when it can develop a diagnostic application (see BioCommerce Week 5/19/2005).

Roche must "move out of PCR — it has finite applications, and molecular testing is evolving into miniaturization, into more sequencing, more patterns, more of that type of thing that PCR can't do," Shara Rosen, an analyst with Kalorama Information, an industry consultancy based in New York, told BCW's sister publication Pharmacogenomics Reporter in May.

However, West questioned the immediate benefits of 454's decision to focus attention on downstream applications, which he said are several years away from gaining traction in the market, and said they should take a back seat to the research community, which is his company's immediate core market.

"Our focus has been, 'How do we get to the whole human genome?'" West told GenomeWeb News at the GMEC conference. It could take years for a company to win regulatory approval for an HIV strain-typing test — even one that has the backing of the world's largest molecular diagnostics company, and even for such a small virus as HIV.

"The real market in the real term is the research market," West said. He added that Solexa has in the past collaborated with drug makers for similar applications for Lynx's MPSS platform, and said he hopes to collaborate eventually with pharmas with the company's sequence-by-synthesis instrument. Solexa merged with Lynx in March.

West reiterated the company's goal of launching the platform by the end of the year and beginning to generate revenue from it, first as a service, by the middle of 2006.

Earlier at GMEC, the company demonstrated that its reversible-terminator chemistry and Clonal Single-Molecule Array technology could be used to sequence a 162,000-base-pair BAC from the HLA region — proof, it said, that the platform can "achieve the data quality, read length, and coverage uniformity required for economical and rapid resequencing of human DNA."

Using 25-base-pair reads, Solexa said its scientists were able to align 90 percent of the BAC back to its own reference sequence, achieving greater than 99.99 percent consensus accuracy in the alignment. Solexa said it was also able to correctly call 100 percent of 153 polymorphisms in the regions.

The work was completed as a proof of concept using "an early laboratory prototype instrument," Solexa said.

In his GMEC presentation, 454's Rothberg said his company's GS 20 instrument, which began being placed earlier this year, is "well on track" to being able to sequence a mammalian genome at 8X coverage for less than $100,000 by the end of 2006. It costs around $1 million to attain this kind of coverage using existing Sanger-style techniques, he said.

Rothberg has in the past said 454 plans to meet the $100,000 genome goal by the end of the year, but hasn't publicly defined the coverage he could generate until now.

A 454 official who wished to remain anonymous told GenomeWeb News at the GMEC conference that the company has so far installed around 14 instruments worldwide, but a CuraGen spokesperson would only confirm the placement of five instruments through the end of June, the company's most recent fiscal quarter. The spokesperson added that the firm did continue to sell additional instruments before its partner Roche Applied Science officially announced the commercial launch of the system earlier this month (see BioCommerce Week 10/13/2005)

— Kirell Lakhman ([email protected])

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