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NanoString Seeks to Supplant qPCR With New Low-Plex, High-Throughput Reagents

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SAN DIEGO (GenomeWeb) – NanoString Technologies has launched a new line of reagents, targeting applications in what it calls the "low-plex" gene expression profiling and genotyping markets.

Announced during its fourth quarter financial results but officially launched in advance of the Association of Biomolecular Research Facilities annual meeting here this week, PlexSet targets a market that has been traditionally dominated by qPCR. 

"It changes the economics for custom projects," NanoString VP of Marketing Anna Berdine said.  Leveraging the firm's optical barcoding strategy, this new offering will require researchers to special order oligonucleotide sequences through a third party, such as Integrated DNA Technologies. Two custom oligos will hybridize to the capture probe and optical barcode, as well as to the target. For researchers looking for a small number of defined targets — more than three and fewer than 20 — in a large amount of samples, it's a new offering that NanoString says can eliminate some of the complexities of optimizing multiplex qPCR reactions.

It's a highly competitive arena, a Thermo Fisher Scientific representative present at ABRF said, who requested not to be named because she was not speaking in an official capacity. A rep from another qPCR instrument maker said the market is largely dominated by Thermo Fisher Scientific brand Applied Biosystems, Roche, and Bio-Rad Technologies. But NanoString is confident that it can take market share, especially at multiplexing levels just beyond what qPCR can easily offer, in the high single- to low double-digits. The firm has estimated the market at around $300 million, and growing every year.

Berdine said that the impetus for launching this product came form existing customers. NanoString is doing it at ABRF because it's a technology that's amenable to the core facility market,. "It's a capability we've had for a while, we're just deciding to commercialize it now," she said.

It's a response to several nCounter customers in the core community, she said. Traditional qPCR gene expression analyses require a lot of sample material and manual labor. "That is what we heard. With previous chemistries, you could do it, but it's not as cost effective as it is now" with PlexSet, she said.

Christian Lytle staffs Dartmouth-Hitchcock Medical Center's (DHMC) Molecular Biology Shared Resource, a National Cancer Institute-funded core facility that serves DHMC's Norris Cotton Cancer Center. His facility has three Applied Biosystems qPCR machines and the cancer center has several more Bio-Rad instruments. "I've never wanted to offer qPCR, I just don't have the time," he said, though he maintains the instruments for researchers to use. "I highly suspect many of them have not done the appropriate controls and validations they need to be doing to do good qPCR work," he said.

He also has a NanoString nCounter machine and was able to test drive the PlexSet reagents prior to launch. "I'm looking at this because you don't have to do the same amount of validation," he said.

With the ability to track fewer than 20 genes, PlexSet represents a new lower limit in the level of multiplexing for NanoString, according to VP of Investor Relations Doug Farrell. "Products we've sold in the past would go up to 800 genes," he said. "I don't think we've sold a set less than 20." But that's a fair amount more multiplexing that qPCR can offer.

There, the upper limit of multiplexing stands at around five or six genes, Lytle said. That's a problem now that gene expression studies use three different housekeeping genes as controls —high-, medium-, and low- expressed genes. "That's three you need to be doing and you haven't even gotten to the ones you want to assay," Lytle said. He said that the limitations of qPCR have been so prominent that researchers won't even design studies for more genes. "They know they don't want to multiplex because of the difficulties," he said. "They're just not crossing that border because they know about the complexities." But with PlexSet opening up the other side of that line, he thinks researchers will want to look into more multiplexing.

Lytle has also tested another application for PlexSet that NanoString is pushing: CRISPR gene editing validation. As CRISPR has taken off at DHMC, he's seen researchers struggle with validating their edits as well as validating the function effects of gene insertion.

With PlexSet, they can now do both in one shot, especially since the protocol works with cell lysates. "They don't have to do cDNA conversion as with qPCR, there's no library prep [as with sequencing]. From a workflow perspective, there's a huge advantage," Berdine said.

Lytle used PlexSet to help validate a cancer gene fusion that a Dartmouth researcher was trying to effect. It turns out the edits weren't successful, but that's beside the point: no longer did that researcher have to do time-consuming Sanger sequencing to check up on CRISPR activity.

NanoString is so enthused about the CRISPR applications that it is offering grants to five researchers to validate up 24 gene targets in 192 samples. Researchers have until May 20 to apply.

From a business standpoint, NanoString does not expect to butt in on the entire $300 million qPCR market opportunity. For researchers looking at one or two genes, they may want to stick with standard qPCR.

But getting up to four, five, six, or more genes is an area where NanoString could become attractive, especially with its 96-well format.

NanoString will be tracking revenue for PlexSet as well as adoption and publications using the reagents.

"It will be an opportunity to drive more pull-through on the existing systems," NanoString CEO Brad Gray said on a conference call where the firm introduced PlexSet. And for labs that don't already have an nCounter system "it could drive incremental [nCounter] Max instrument sales," he said.

For core facilities like Lytle's, the CRISPR validation is another service to offer researchers and help keep him afloat. "I'm really exited about this," he said. "It gives me another place to branch out."

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