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Olink Genomics Launches Targeted Resequencing Service, Plans to Debut Reagent Kits

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By Justin Petrone

TALLINN, Estonia — Swedish startup Olink Genomics this month began offering a service to that uses its multiplex amplification technology to select DNA for sequencing with second-generation technologies, according to a company official.

CEO Olle Ericsson also said this week that Olink is seeking early-access customers for reagent kits that use the firm's Selector Technology, and that it plans to begin selling reagent kits to customers early next year. BioArray News spoke with Ericsson during the Human Genome Variation and Complex Genome Analysis meeting, held here over the weekend.

Olink, a subsidiary of Uppsala-based Olink Bioscience, was founded to commercialize technology developed by researchers from Olink Bioscience and Uppsala University. Olink Genomics was founded as a subsidiary to enable its parent Olink Bioscience to focus on commercializing a technology for protein-interaction analysis called proximity ligation assay, or PLA.

By entering the target enrichment market, the firm will compete with Agilent Technologies, Febit, Fluidigm, LC Sciences, RainDance Technologies, and Roche NimbleGen.

Ericsson said that Olink officially launched the service this month. "Right now, we are offering sample preparation as a service so customers can send their samples to us and we prepare the samples and send back the enriched DNA," Ericsson said. The firm's first customers tend to be "genome centers or people who have an order of 50 to 500 genes that they want to resequence in 10 to 1,000 patients," he said.

"Really, where we want to take this technology and where its strength is, is to have reagent kits," Ericsson added. "That's where you really can utilize the advantages of it, when you take the samples and prepare them yourself."

Ericsson said that in the "slightly longer term" Olink Genomics will offer targeted amplification of larger regions like the whole exome, though demand has not yet materialized. "At the moment these projects involve too much sequencing and too little sample preparation to be really interesting for us, but this will likely change in the coming year or so," he said.

Olink's Selector Technology uses multiplex amplification with Selector Probe libraries of oligonucleotides to enrich thousands of genomic target fragments in a reaction tube, according to the firm. A DNA sample is first fragmented by restriction enzyme digestion, and then denatured. The Selector Probe library is added and the probes hybridize to the targeted fragments. Each Selector Probe is designed to hybridize to both ends of a targeted DNA restriction fragment, which guides the targeted fragments to form circular DNA molecules. The circular molecules are then closed by ligation and amplified, providing users with an enriched amplification product that can be sequenced by any second-generation instrument.

Ericsson said that Olink's Selector Technology combines the specificity of PCR with the scalability of a solution-phase amplification protocol. "The problem with PCR is that you cannot combine several primer pairs in one tube, but the compromise that you do when you go into hybridization is that you only have one probe per target, so you lose some of the regional specificity that PCR has," Ericsson said.

"We have an approach where we have one tube containing one probe that captures two sites on each target," he said. "We solve the specificity problem and we maintain the simplicity of combining throughput and performance that you need to do large-scale resequencing."

Competitive Landscape

Olink joins the market for front-end applications for targeted resequencing at a time when other firms, both large and small, have spent months trying to win a chunk of what both businesses and customers think will be a profitable sector.

For a year and a half, Roche NimbleGen has sold a sequence-capture service that is based on its microarrays and the company is now developing an in-solution sequence capture application for higher-throughput studies (see BAN 7/14/2009).

Agilent and Heidelberg, Germany-based Febit, meantime, entered the market within weeks of each other earlier this year.

Agilent initially launched its in-solution-based SureSelect target enrichment system in February, but rolled out an on-array target enrichment application in July for lower-throughput studies (see BAN 2/10/2009, BAN 7/14/2009).

Febit launched its HybSelect application for targeted resequencing in February and in July launched a catalog cancer biochip for targeted DNA capture. The new chip features 115 genes reported to be associated with common types of cancer by the Wellcome Trust Sanger Institute (see BAN 2/17/2009, BAN 7/14/2009).

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Also in July, Lexington, Mass.-based RainDance Technologies launched its own sequence enrichment application. RainDance's technology sets up millions of PCRs in picoliter-sized droplets and combines them in a single vial for PCR amplification, according to the company.

More recently, Houston's LC Sciences and South San Francisco, Calif.-based Fluidigm launched chips and services for customers that want to do targeted resequencing.

In March, LC Sciences began offering its Target-Specific Selection service for the capture of a defined genomic region or RNA sequences. The service is based on the firm's µParaflo biochip technology (see BAN 3/3/2009).

And in June, Fluidigm launched Access Array, an integrated fluidic circuit designed to support high-throughput re-sequencing, targeted enrichment, sample barcoding, and library preparation for sequencing using amplicon tagging (see BAN 6/16/2009).

Despite this crowded field, Olink Genomics' Ericsson said the company has "lots of reasons" to enter the market. "We think we have a strong IP position, the technology is very promising in solving an important problem, and commercially there is a great need in the big market," he said at the Estonian conference.

"We had a lot of talented people in the area that could work on it and commercialize it. All of these factors came together and made us make the decision to start the company," he said.

Ericsson also said that just because a number of companies are targeting the same space doesn't mean that they are always competitors. The size of a customer's study, for example, could dictate whether they choose to use the Selector Technology or go with a different company's platform.

"Since we have a scalable technology, we fit in where you need to do many samples since we can use microtiter plate formats," Ericsson said. "We can also address customers that don't want to buy expensive instrumentation," he said. "Our instrument is basically a microtiter-welled plate and tube. That is the infrastructure investment, which is not that significant."

Other conference attendees agreed there is plenty of opportunity in what is varyingly referred to as the target capture, sequence capture, targeted resequencing, or target enrichment market.

"Targeted sequencing is very interesting and very useful and can be used in different sectors," said Stephen Chanock, a senior investigator at the National Cancer Institute. "I think it's a very exciting endeavor. Having enrichment is an important step. The question is how efficient you make it and at what cost," Chanock told BioArray News. "We on the academic side are interested in seeing how these resources develop in a way that will be both efficient and economic."

Pui-Yan Kwok, an investigator at the Cardiovascular Research Institute at the University of California in San Francisco, said he believes "a lot of people will start using target resequencing approaches to quickly scan all these genes" identified in genome-wide association studies. He told BioArray News that his lab is currently using RainDance's platform. "PCR is a mature technology. I think the chances of success are higher," he said.

"For some applications it's the right thing to do, for others it's not," said Andreas Gnirke, an investigator at the Broad Institute. "It's technically feasible, economically viable, and scalable," he told BioArray News. "For many projects, this is logical; it's what you have to do. This community has to do this," said Gnirke. "How much can companies actually make doing this though? I don't know," he said. "They'd probably make more money developing drugs."

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