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Looking at Anybody Who Would Talk to Us, ABI Finds VisiGen

NEW YORK, Oct. 31 (GenomeWeb News) - As the genomic community continues to buzz about emerging next-generation sequencing technologies, it has started to get a taste of what's to come from shops such as 454 Life Sciences and Solexa.


At the same time, industry insiders had begun to speculate why Applied Biosystems hasn't announced any big moves to advance its play in an area it has dominated for years. Then last week, the company said it would acquire an undisclosed stake in VisiGen Biotechnologies and help the fledgling tool shop develop its single-molecule sequencing technology. Whether ABI invests in VisiGen hinges on the fulfillment of certain seemingly unorthodox conditions.


To be sure, ABI has recently disclosed that it has been developing its own next-generation sequencing technology, including one based on a cluster approach. But its decision to partner with and buy a chunk of VisiGen -- not to mention the lengths to which it went to pen the alliance -- indicates it's not just going to rely on its own assets.


Before making its move, ABI said it considered many researchers and companies developing alternative sequencing techniques. "We've been looking at everybody, anybody who would talk to us," Kevin Corcoran, vice president and general manager of ABI's genetic analysis business unit, told GenomeWeb News last week.


He said ABI had identified around 30 companies involved in developing new technologies. Though ABI declined to name the companies, possibilities could include Solexa, Helicos, Nanofluidics, AQI Sciences, SeiraD, Agilent, Microchip Biotechnologies, Li-Cor, and Quiatech.


So why VisiGen? The company's approach involves engineering both polymerase and nucleotide triphosphates to act together as direct molecular sensors of DNA base identity in real-time. Though the company has been optimistic about its goal to deliver human genome sequencing for $1,000, it has released little data about where its research stands or provided proof of principle to the public by sequencing an organism.


This contrasts with companies such as 454, which has a platform on the market, and Solexa, which said it will release its instrument by the end of year. Two weeks ago, to show the sequencing community that its technology is getting traction, Solexa said it has used its single-molecule array technology to sequence a human bacterial artificial chromosome.


Corcoran said ABI would invest in VisiGen because of its sequencing approach. ABI "is interested in the single-molecule approach," said Corcoran. "Solexa is not taking that approach."


He said ABI worked closely with VisiGen and "reviewed a lot of their data" before deciding to pursue an investment. "I don't want to disclose how far along they are, but they've made significant progress," Corcoran said. ABI would only say that its investment and collaboration are subject to certain conditions, including one that specifies VisiGen must receive an additional  investment from SeqWright. On its face, this is an unusual requirement because companies of ABI's size -- the firm generated $1.8 billion in revenues last year -- seldom rest tech investments on financial plans made by small, privately held vendors.


In this case, ABI would be VisiGen's second investor. Last fall, SeqWright made an undisclosed equity investment and entered into a scientific collaboration with the company. VisiGen and SeqWright are based in a Houstonbiotech park and are part of the same holding company, BioWright, according to VisiGen's web site.


Ken Paynter, operations manager of SeqWright, said that when his company made its original investment, VisiGen provided proof of concept. He also said there's been significant progress since then.


"Our founder, [Richard] Gibbs, went in and worked with it, and then, with his involvement, there was some immediate improvement in the technology. It is a matter of scaling it up and commercializing it at this point," Paytner said.


Eugene Chan, who recently reviewed advances in sequencing technologies in the journal Mutation Research, said ABI's move is not surprising. "I think VisiGen has made progress as a company over the past few years," said Chan, an investigator at the DNA Medicine Institute in Bostonand founder of the erstwhile sequencing company US Genomics, which has Craig Venter as director.


However, Chan, like most industry watchers, is skeptical that the $1,000 genome is around the corner. "There are significant challenges in read length for all currently proposed methods, which will limit their utility to small genomes," he told GenomeWeb News. "There still needs to be some major breakthroughs to accomplish the $1,000 genome goal. It is very likely that the approach that will reach this goal will be a technology that has yet to be invented."


So far, the only new sequencer to actually appear on the market is 454's machine, which promises to deliver sequencing 100 times faster than current methods.


Indeed, ABI has taken these steps as the race heats up to develop technology that will reduce the cost of sequencing a mammalian genome to $100,000 or even $1,000. In the last year, it's become increasingly clear that those already in the sequencing game don't want to get left behind.


Beside ABI and its VisiGen overtures, Beckman Coulter acquired Agencourt Biosciences, which is developing sequencing technology based on the polony approach pioneered by George Church at Harvard. GE Healthcare, which last year acquired Amersham and its MegaBACE technology, said it's continuing to evaluate all of its options to develop new sequencing tools, including partnering.


Visigen was founded in 2000 by Susan Hardin, an assistant professor of biology at the Universityof Houstonand five other researchers at UH. The company was originally funded with grants from the Defense Advanced Research Projects Agency and the National Institutes of Health. Most recently, it received a $4.2-million grant from the National Human Health Genome Research Institute.

Kate O'Rourke, a Genome Technology reporter, covers DNA sequencing for sister publication GenomeWeb News.

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