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New Olink Bioscience Business to Sell Multiplex Amplification Service in 2009

Olink Bioscience said last week that it has teamed up with researchers at Uppsala University to found a subsidiary, Olink Genomics, to sell a multiplex amplification technology to select DNA for sequencing with second-generation technologies.
The early-stage Swedish company is joining a number of other firms, among them Roche NimbleGen, Agilent Technologies, and Febit, that are commercializing related DNA capture or selection technologies for sequencing.
Olink Genomics was founded in August by Olink Bioscience and four scientists from the research groups of Ulf Landegren and Mats Nilsson at Uppsala University. The firm is currently supported by an undisclosed amount of funding from government grants as well as private investors.
Currently housed at Olink, the company, which has no full-time employees yet, next year plans to move into its own space and start offering a sample preparation service for sequencing, according to Olink Genomics president and CEO Olle Ericsson.
Olink Genomics will focus on commercializing so-called Selector technology, a multiplex amplification method, for use with second-generation sequencing technologies, for example in cancer resequencing projects. In May of last year, several of the Uppsala researchers, in collaboration with scientists at the Stanford Genome Technology Center, published a paper in the Proceedings of the National Academy of Sciences describing the approach (see In Sequence 5/22/2007).
Both Landegren and Nilsson are co-founders of Olink and ParAllele Bioscience, which is now owned by Affymetrix. Landegren has joined Olink Genomics’ scientific advisory board and Nilsson is a director (see Paired Ends, in this issue).
The reason Olink Genomics was founded as a separate subsidiary is that Olink will focus on commercializing a technology for protein-interaction analysis called proximity ligation assay, or PLA.
Olink Genomics also gained access to additional intellectual property, software, and technology know-how from the academic co-founders, according to Ericsson.
The Selector technology uses two oligonucleotide probes for each target to be amplified. A selector probe with a general primer pair motif in the center has ends that are complementary to the target sequence. A vector oligonucleotide binds to the general primer motif of the selector probe. A description of the approach is available on Olink’s website here.
In their proof-of-principle study published in PNAS last year, the Stanford and Uppsala researchers showed that they were able to use the Selector technology, coupled with 454’s sequencing platform, to amplify and sequence 10 genes comprising 177 exons from cancer cell line DNA.
Since then, the Uppsala researchers have increased the technology’s performance, according to Ericsson. “Definitely, we have been improving it to get even representation of the targets,” he said, but declined to reveal specifics.

“The complementarity of the new sequencing technologies for deep resequencing of cancer is very attractive.”

Olink Genomics has several ongoing collaborations with undisclosed academic groups, he added, but it is “not actively” working with the Stanford team anymore.
Though the company does not currently own a second-generation sequencer, initially it will have access to the technology through commercial vendors and collaborations with the Uppsala University genome center, which has two Applied Biosystems SOLiD instruments, according to Ericsson. Also, another research group at the university owns an Illumina Genome Analyzer.
The company will focus on cancer exon sequencing as its first application. “The complementarity of the new sequencing technologies for deep resequencing of cancer is very attractive,” said Ericsson, who completed his PhD in Landegren’s lab earlier this year and is still an affiliated scientist at the Rudbeck Laboratory at Uppsala University.
“Our first goal is definitely the approximately 100 to 1,000 cancer genes,” he said. A long-term goal is to sequence all exons in a genome, as well as other selected genome sequences.
Later this year, the company plans to start testing its technology as a service for trial customers, followed by a regular sample preparation service in early 2009, according to Ericsson.
Later in 2009, the firm also wants to start offering both standard and custom reagent kits for sample preparation.
Roche NimbleGen, Agilent, Febit
Olink Genomics is not the only company to offer services for target enrichment for sequencing. This spring, for example, Roche NimbleGen began selling a sequence-capture service that is based on the company’s microarrays (see In Sequence 4/8/2008). Last week, the company said the capture arrays are now also for sale to researchers (see New Products, in this issue).
Also this spring, Agilent Technologies said it had licensed a method from the Broad Institute (see In Sequence 5/13/2008) that involves biotinylated long RNA probes and is based on its Oligo Library Synthesis technology. An Agilent spokesperson told In Sequence last month that this technology is “still on track for a November launch.”
And last month, Febit said it is testing its HybSelect DNA capture service, which involves its own microarrays, in collaboration with the Translational Genomics Research Institute and plans to commercialize the technology in early 2009 (see In Sequence 8/19/2008).
However, Ericsson believes the Selector technology has an edge over these other methods. For example, because Selector amplifies the targets rather than just enriching them, it is possible to use less starting material than array-based approaches. Thus, researchers might be able to use clinical samples, such as formalin-fixed paraffin-embedded material, which “is something we will be working towards,” he said.
The technology is also easier to automate and scale than array-based approaches, he claimed. “If you want to run 1,000 samples, [microarray capture] is not really amenable for automation in a straightforward way, compared to solutions where you use reaction tubes and 96-well plates,” he said.
Unlike microarray capture, the Selector technology also does not require specialized equipment, for example a hybridization station. “You need a PCR machine, that’s it,” he said.
Finally, Ericsson said that the use of a ligation step in the Selector technology improves selectivity, compared to hybridization-based approaches. “Working with hybridization, I think there will always be a compromise between hybridizing selectively to the target and still capturing, for example, indels or variations in your target that you are actually looking for,” he said.

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