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Estonian Microarray Startup Hopes to Capture SNP Market

NEW YORK, March 2 - Tartu, Estonia may seem an unlikely launch point for a global assault on the SNP chip market. But Asper Biotech, a small Estonian microarray startup, hopes to leverage its unique chip-based sequencing technology to do just that. 

"Asper's edge is that manufacturing on a chip and reagent costs are way lower," than other SNP sequencing methods, said Kalev Kask, director of Asper's US office. "Our cost is definitely below 50 cents a SNP right now."  

Asper can currently fit more than 30,000 oligos on a chip, Kask said. But it plans to substantially increase that number, reduce its cost-per-SNP, and in doing so beat out competitors like Orchid and Sequenom.  

Asper also says it can undercut custom chip designers like Affymetrix because it uses oligonucleotides, not photolithography. Oligos, said Kask, "are pretty cheap these days."  So far, the company has developed a p53 tumor suppressor gene chip, and plans to publish a paper in a major scientific journal on the use of this chip to detect mutations in the p53 gene. But it has not yet gained a license to the p53 gene to commercialize this chip. 

The company's microarray technology, which was developed by Andres Metspalu of the Estonian Biocenter, is based on the Sanger sequencing method, where a polymerase is used to extend one strand of DNA primed by other strands off of a chip, Kask said.  

The oligonucleotides sticking out of the glass chip hybridize to the sample DNA, then a polymerase and a fluorescent terminator are added. The fluorescent terminators are four colors - blue, green, red, and yellow - each corresponding to a DNA nucleotide.  

"The fluorescent terminator nucleotides are synthesized so they are just one nucleotide from the site of the expected mutation, which gives you an exact readout of what is at the site of the mutation,"  Kask said.  

This feature gives the chip a higher signal-to-noise ratio for increased reading accuracy. Each oligo is also repeated on a chip to improve readout, so sequence appears on the chip as a series of paired circles in these four colors.   

Since its founding two years ago, Asper has hired over 35 employees, raised $2 million in financing from American and Estonian venture capital firms, and attracted nine customers. The company is currently seeking out $5 million in a second round of financing and working out plans for an American distributor of its chips.  

But it may find its largest customer in its own backyard. Since the 1960s, when Estonia was part of the Soviet Union, it has been a hub of microbiological and biotechnological research, and there are currently over 400 scientists working in the field there, said Kask. 

In August 2000, the Estonian Genome Foundation and the Government launched the Estonian Genome project, an effort to create a population genetic database that includes 100,000 SNPS per person for 1 million of Estonia's 1.4 million people; then conduct SNP association studies that link genetic variations in that population to cancer and other disease susceptibilities, and sell this information to drug and biotech companies.  

Asper has submitted a proposal to the Estonian Genome Project to do sequencing, and expects to hear from the project in late summer. 

"Since Asper has the technology on the ground it has the first mover's advantage,"  Kask said. "It is well placed to capture the market."  

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