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Olink Seeks a Piece of the Protein-Array Market with Proximity Ligation Technology

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Olink Bioscience, a small Swedish startup with a novel technology, has set its sights on the already crowded protein array market. Based on a technology that captures proteins in solution, rather than on a chip, and uses DNA as a reporter signal, the company promises higher sensitivity, better specificity, and more multiplexing capabilities than competitors’ products.

But it remains to be seen whether Olink will be able to capture a significant portion of the research or diagnostic market.

“There is a lot of stiff competition,” said Steven Bodovitz, a consultant with BioPerspectives who has been tracking the protein chip market. “All the different protein biochips, almost all have something clever about them.”

Olink was founded in September and holds exclusive licenses to a portfolio of DNA-based detection and amplification technologies developed in the laboratory of Ulf Landegren at Uppsala University. The company plans to develop and commercialize one of them — called proximity ligation — for protein analysis applications. Another one — padlock probes — has already been licensed to ParAllele Biosciences in San Francisco.

Olink’s protein analysis technology requires pairs of antibodies, each with an oligonucleotide attached, that recognize two different sites on the same protein. When both antibodies bind to their target in solution, the oligos come in close proximity and can be connected by a hybridization ligation reaction. The joint DNA can then be amplified and be used as a readout signal. Multiplexing the reading step is possible by hybridizing the DNA signals to a standard DNA tag array.

“With these dual recognition events, the background is dramatically reduced,” said Björn Ekström, Olink’s CEO, who used to head R&D at Pyrosequencing, and held R&D positions at Amersham Biosciences and Pharmacia Biotech. “We get very high specificity, low background, and incredible amplification.”

This, he believes, sets the technology apart from that of competitors. Other companies, such as Molecular Staging, have already exploited DNA as a readout for protein detection using rolling circle amplification. However, their reporter DNA is attached to one, not two, molecules.

In addition, Olink’s technology does not require custom-made equipment, such as microarrays or scanners. “We can reach the market very quickly since we don’t need any specialized new equipment,” Ekström said. “Everything that we have today is smart chemistry that can be implemented on a variety of different systems.”

The need for such equipment might have contributed to the demise of others, such as Zyomyx, which recently laid off almost all of its employees after developing sophisticated protein chips and instrumentation for years.

“Price is more important than many of these companies realized,” said Bodovitz, adding that a lot of protein array platforms can already use standard equipment, such as DNA microarray scanners.

However, Olink still shares a major challenge with all the other protein array companies: having available pairs of good antibodies or other binders for each target.

“That is definitely the bottleneck right now,” Ekström admitted. “Everything hinges on the quality of the binders you are using. If you have low-performance binders, our method can only take you that far.” However, Olink is optimistic: the company is betting on both commercially available antibodies, and it is collaborating with several undisclosed organizations that are developing binding agents.

Olink plans to enter the research market with its first products by mid-2005: assays for single proteins in low concentrations, for example signaling proteins. After that, the company wants to develop multiplexed assays for panels of analytes. In addition, it hopes to enter the diagnostic market by developing analyte specific reagent kits for early diagnostic tests, for example for cancer. This would be most likely in collaboration with “an established diagnostic partner,” Ekström said.

But the path to commercialization is still far away. At the moment, Olink, which has four employees, is trying to raise venture capital and is in discussions with Swedish and international VC firms.

The company has approximately 1.6 million Swedish kronors ($225,000) in seed financing from Uppsala University Holding Company and from the seven founders.

— JK

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