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Roche Launches 454 Sequencer as Industry Takes Shape and Rivals Scramble to Catch Up

454 Life Sciences and its marketing partner, Roche Applied Science, announced last week that they had launched 454's new DNA sequencer, the first of a new wave of competing sequencing technologies expected to hit the market over the next year.

Though these newer, alternative sequencing instruments have garnered quite a bit of attention — and money from the US National Human Genome Research Institute — they have a long way to go before replacing the standard capillary electrophoresis platforms sold by market leader Applied Biosystems and rivals GE Healthcare and Beckman Coulter. However, the potential of these newer technologies to eventually slash the cost of sequencing a mammalian genome from roughly $10 million today to $1,000 has made the makers of standard CE sequencers take notice and action.

ABI President Cathy Burzik recently acknowledged for the first time that the firm is working on its own next-generation sequencing technologies (see BioCommerce Week 10/6/2005). Though she declined to provide specific details, Burzik said ABI has "a number of approaches under development," including a cluster approach.


GE said it is "definitely looking at alternative technologies and continue to evaluate all the options. Of course, we may partner with an appropriate organization if it makes sense. We are committed to staying in sequencing."

ABI officials, though, have repeatedly stated that the newer technologies are not going to make an impact over the next couple of years, and the firm does not see an end to the dominance of capillary electrophoresis in the DNA sequencing market. As evidence, ABI cited the June sale of 20 of its 3730xl capillary electrophoresis DNA sequencing instruments to the Broad Institute, bringing the institute's total installed base of this type to 126.

Like ABI, GE has been relatively quiet on the subject of newer sequencing technologies. GE, which sells Amersham's legacy MegaBACE line of sequencers, is considered a distant second in the sequencing instrument market, and is keeping an eye on the emerging technologies.

"We are definitely looking at alternative technologies and continue to evaluate all the options," Nicola Raw, head of marketing for research, consumables, and equipment at GE Healthcare, told BioCommerce Week via e-mail. "Of course, we may partner with an appropriate organization if it makes sense. We are committed to staying in sequencing."

Earlier this year, CE sequencing rival Beckman acquired Agencourt Bioscience, which is working on a sequencing-by-synthesis approach, for approximately $140 million (see BioCommerce Week 5/5/2005). The sequencing method is based on the polymerase colony amplification technology developed in the lab of George Church at Harvard's Lipper Center for Computational Genetics and licensed to Beckman in 2004.

Beckman has yet to disclose a timeframe on when Agencourt's instrument will hit the market. According to a spokesperson, the firm will offer DNA sequencing services with the technology first, followed by a product launch.

454 Beats Rivals to the Market

454, which is a unit of New Haven, Conn.-based biopharmaceutical company Curagen, is widely considered to have the most advanced of the new DNA sequencing technologies. A prototype of its massively parallel sequencing instrument, the Genome Sequencer 20 System, has been in use at the Broad since March. That was followed by the US Department of Energy's Joint Genome Institute's August purchase of 454 sequencing instrument at a cost of $500,000.

According to the firm, the Genome Sequencer 20 can sequence at least 20 million base pairs in a five-hour run. 454 said the instrument eliminates the need for large-scale robotics for colony picking and sample handling.

Roche is selling the instrument and related reagents worldwide under an exclusive agreement with 454 inked in May (see BioCommerce Week 5/19/2005). The Swiss diagnostics giant has rights to sell the platform in all markets except regulated diagnostics. However, Roche holds exclusive rights to negotiate an extension of the agreement to include the regulated diagnostics market during the initial five-year term of the pact.

The deal is potentially worth $62 million to 454, and the commercial launch of the instrument triggered a $7.5 million milestone payment from Roche. But it could also mean a large payoff for Roche in the future, particularly as a hedge that 454's technology could play a role in molecular diagnostic applications.

With the 454 alliance and a previously announced pact to sell gene expression-analysis technology from Exiqon, Roche will undoubtedly have a significant impact on many research instrument manufacturers looking to cross over into the molecular diagnostics market in which it is the leading player.

Meanwhile, a handful of 454 competitors are scrambling to catch up and get their own instruments on the market. In addition to Agencourt, Solexa and Helicos BioSciences expect to launch their sequencing platforms within the next year.

Solexa CEO John West told BioCommerce Week that the firm expects to ship initial units and recognize revenue in the first half of 2006. He said the instrument would cost around $400,000, and the cost of resequencing a human genome with Solexa's technology would be under $100,000.

David Bentley, Solexa's chief scientist, told BioCommerce Week sister publication Genome Technology in August that the technology would soon enter alpha production, which means that labs could be paid for the insights they offer the company. According to Bentley, "enthusiastic" alpha collaborators include Jane Rogers at the Sanger Center, Rob Mitchell and Eric Lander at the Broad, Rick Wilson and Elaine Mardis at Washington University, and Rob Waterston at the University of Washington.

West noted that thus far no instruments have been placed with external researchers or sequencing facilities, but the company is working internally on customer-provided samples.

Helicos expects to ship its cyclic sequencing-by-synthesis instrument to Lander's lab by the end of the year, according to Genome Technology, and Lee Hood, president of the Institute for Systems Biology, recently said the Institute may test one of Helicos' prototypes. Hood serves on Helicos' scientific advisory board along with George Church, the inventor of the technology used in Agencourt's platform. Helicos plans to have beta instruments out by next year and a commercial system available in 2007.

In addition to these companies, there are several other small firms and researchers working on their own alternative sequencing technologies. Their efforts have been given a big boost by the NHGRI, which has awarded $70 million in grants over the past two years to support development of the technologies.

— Edward Winnick ([email protected])

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