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NanoString, MD Anderson Partner to Combine Genomic, Proteomic Assays on nCounter System


NEW YORK (GenomeWeb) – NanoString announced this week its plans to move into proteomics by forming a multi-year collaboration with the University of Texas MD Anderson Cancer Center to develop and implement assays for simultaneously measuring gene and protein expression on its nCounter Analysis System.

The company plans to beta launch an initial multiomic assay this month at the American Association of Cancer Research annual meeting in Philadelphia, and launch additional assays later this year, NanoString President and CEO Brad Gray told GenomeWeb.

The MD Anderson collaboration will focus on developing assays to profile key cancer pathways and patient immune response, which MD Anderson researchers will then use to predict and monitor response to cancer therapies and immunotherapies, in particular, Gray said.

NanoString will hold the rights to research and diagnostic content generated through the collaboration.

The multiomic assay stems from research at Massachusetts General Hospital into using NanoString's nCounter Analysis System for protein analysis. In a study published last year in Science Translational Medicine, MGH researchers led by Ralph Weissleder developed an approach to protein quantitation using antibodies linked to photocleavable DNA barcodes. These DNA-linked antibodies detect the proteins of interest, upon which the DNA barcode is released and can then be quantified by the nCounter platform.

Speaking to GenomeWeb upon publication of the study last year, MGH researcher and paper author Cesar Castro noted that nCounter was an appealing readout system due to the fact that its fluorescence hybridization approach offers high multiplexing and quick turnaround time while requiring no amplification.

NanoString licensed the IP to the technique from MGH and, Gray said, has been working to develop the approach to measure both genomic and proteomic markers simultaneously.

"What we have done over the year since [the MGH team] published the [STM] paper is find a way to reduce to practice the technique described in that paper to not just to look at proteins but to look at proteins and gene expression simultaneously in the same sample," he said.

"What we've developed is a workflow that allows us to count the RNA targets and the barcodes from the antibodies all in the same assay, just [using] two different types of barcodes," he added.

NanoString now aims to further develop the platform and assays in concert with MD Anderson researchers led by Gordon Mills, chair of systems biology at the center. Despite the fact that the initial IP was developed at MGH, Gray noted that MD Anderson is a leading cancer research center with a number of labs using the nCounter system.

He also cited Mills' experience working with genomics and proteomics in cancer research. Indeed, Mills has been the leading researcher on the proteomic side of the National Cancer Institute's Cancer Genome Atlas (TCGA) initiative, which has built genomic and proteomic profiles of a wide variety of cancer types.

Several months ago, NanoString researchers demonstrated the ability of the platform to look at roughly 750 messenger RNAs, 30 proteins, and several gene fusions simultaneously, Gray said. The initial assay developed through the MD Anderson collaboration will feature around 770 mRNAs and 30 proteins and will focus on cancer immunology, he added.

Essentially, Gray noted, this initial assay consists of the company's existing 770-mRNA cancer immunology panel with protein content added on top.

"What we have the chance to do is verify that what people are seeing in the gene expression domain is actually representative of what is happening at the protein [level], which, of course, we know is not always true," he said. "So what we are doing … at least in the first embodiment of these multiomic experiments is selecting some of the most important proteins for cancer immunology and really probing both the protein and messenger RNA for those important makers."

In future assays, the partners will look to add proteomic markers for measuring events like phosphorylation that are not apparent at the genomic level.

"You can imagine that by looking at levels of important [genomic] drivers of tumor growth you can infer what the pathway dysregulation of that tumor is, and then in the same experiment by looking at phosphorylation events and cell signaling you can confirm that that is actually the exact activation that is happening at the protein level," Gray said, adding that NanoString aims to launch such assays towards the end of the year.

In an email to GenomeWeb, MDAnderson's Mills said he thought "the key power of the approach will be in the ability to collect genomic and proteomic data on the same samples."

"The ability to correlate DNA, RNA, and protein changes in a single assay is expected to provide much more information on heterogeneity, pathways and signaling systems," he said. "We believe that these will provide highly complementary information."

Upon publication of the MGH group's paper last year, Castro compared the technique to reverse phase protein arrays, which similarly use antibodies to measure proteins and protein signaling. A big user of RPPA, Mills noted that the NanoString method would allow for similar measurements but be both faster and more expensive.

A potentially significant advantage, he noted, is the possibility of working with much smaller numbers of cells than is possible with RPPA.

Indeed, in the original STM study, the MGH researchers used the approach for single-cell protein measurements. Gray said this week that the company's initial multiomic assays would not go down to the single-cell level, but that this was a goal down the road.

In terms of multiplexing, while the nCounter system can look at up to 800 analytes at a time, on the protein side multiplexing will be limited by antibody cross-reactivity, Gray said. "You have to find antibodies that play nice with each other and validate that they are working, so that's what drives the number of proteins we would look at [simultaneously]."

In the STM paper the MGH team managed to multiplex around 90 proteins in an assay.

With the move, NanoString joins, most prominently, Fluidigm, as a genomics company moving into the proteomics space.

Fluidigm made its biggest splash in this space with its $207.5 million acquisition in January 2014 of mass cytometry firm DVS Sciences and its multi-parameter single-cell protein analysis platform, the CyTOF 2.

The company also signed a co-marketing deal with Olink Biosciences in July 2013 that combined the two firms' tools to create a high-throughput proteomics platform. In addition to the DVS purchase, Fluidigm plans this year to launch a single-cell proteomics imaging platform based on the CyTOF instrument.

In past interviews with GenomeWeb, Fluidigm President and CEO Gajus Worthington has noted that interest from the company's existing genomics customers informed its move into proteomics.

Customer input made it "abundantly clear that to really do single-cell biology it is a requirement to have genomic and protein analysis," he told GenomeWeb last year.

Speaking this week, Gray sounded a similar note, saying that adding proteomics to the company's assays was "really strengthening our value proposition for our existing customer."

Roughly 75 percent of the new nCounter systems sold in 2014 went to cancer researchers, Gray said. And, according to the company's own internal market research, roughly 85 percent of cancer researchers use both genomics and proteomics in their work.

"Typically they do that by taking the sample and splitting it across two different experiments on two different platforms," he said. "What we are really offering that cancer researcher is the ability to run both the proteomics and genomics on the same platform and thereby get more biology out of the very precious tissue sample they have for their experiment."