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FEATURE: Need a Gene? Blue Heron Plans to Turn Gene Synthesis into a Well-Oiled Machine

NEW YORK, June 1 - Investigating a gene's function, scientists agree, requires a physical copy of that gene's DNA. Sounds simple enough. But just getting enough copies of a gene to use in the lab can often take months of effort, and sometimes, in the case of rarely expressed or otherwise uncooperative genes, efforts to produce the gene's DNA are futile.

Blue Heron Technology, a genomics startup based in Bothell, Wash., hopes to change that. The company was founded last year by John Mulligan, who experienced these difficulties firsthand while a scientist at Darwin Molecular, a Seattle-based company now a part of Chiroscience. Together with John Tabone and Gregg Brickner, two other colleagues from Darwin Molecular, Mulligan set out to industrialize the process of synthesizing full-length genes, and this week the company said it had formally launched its high-throughput gene synthesis platform.

Typically, producing a gene requires either fishing a gene from a cell's nucleus using a specially-designed probe, cloning short segments with PCR, or building the DNA sequence base by base. But in the case of so-called rare genes--those that are only seldomly expressed by the body--the easiest way to produce the gene is to build the DNA synthetically.

What Blue Heron hopes to do, said Peter Nicholson, the company's CEO, is convince customers that Blue Heron can synthesize large numbers of any gene--up to 10,000 base pairs long--cheaper than the customer could itself and within a month to two months.

"We're focused on turning this [technology] into a high-throughput industrial process, that is 100 percent accurate and exceptionally reliable," said Nicholson. 

How Blue Heron does this is proprietary, of course. Traditional oligonucleotide synthesis is well-known and highly automated, Nicholson said, but the technology can't build DNA strands longer than about 100 base pairs, and the sequences often contain random errors. Blue Heron's technology can build DNA sequences 100 times longer, and are guaranteed to be accurate, Nicholson said.

Although the company is young, its roster of supporters is impressive. Leroy Hood, the director of the Institute of Systems Biology in Seattle, Alan Smith, the director of the Protein and Nucleic Acid Facility at Stanford University, and David Galas, the chief academic officer at the Keck Graduate Institute in Claremont, Calif., provided the company's seed investment in 1999. In December 2000, several venture capital firms, including Crabtree Ventures and Integra Ventures, followed suit with a $2.7 million private financing round.

"The management team is what attracted us initially," said Hans Lundin, a managing partner at Integra Ventures. "And we spoke with people who know Mulligan who said he could pull it off." The heavyweight scientific team of seed investors gave the company further credibility, Lundin added.

Those involved with the company have hopes that the market for outsourced gene synthesis services will blow up. Nicholson thinks the market for Blue Heron's services has the same potential as that of DNA microarrays, currently estimated by some to reach about $900 million this year, especially when customers begin to see the advantages the company's services offer. Lundin takes a more restrained view, calling gene synthesis services a "way to make research more efficient" with significant value proposition.

Blue Heron is not alone, however. Six year-old Aptagen, a competitor based in Herndon, Va., says its technology is just as powerful as Blue Heron's and can "maximize the utility" of the genes it synthesizes by tailoring the codons of the gene to suit the species in which the gene will be expressed, said Tony Fitz, a scientist with the company.

Mulligan and his team, for their part, don't plan to stop with gene synthesis. The company has plans to industrialize other biological processes, to further accelerate genomics research. "Keeping scientific projects ontime is critical, and Blue Heron is playing a part in making that happen," Lundin said.  

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