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Proteovista Nets $643K NIH Grant to Develop Array Platform for Cardiac Biomarker Discovery

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NEW YORK (GenomeWeb) – The National Institutes of Health has awarded Proteovista a two-year, $643,000 grant to develop a new microarray platform for identifying biomarkers associated with various cardiovascular diseases.

Based in Madison, Wis., Proteovista was initially called Illumavista Bioscience until it changed its name in August 2013 following a legal dispute over the moniker with San Diego-based Illumina.

The company's core technology is called the specificity and affinity for protein, or SNAP, microarray. Proteovista claims the tool can provide insight into the sequence specificity of any DNA-binding molecule by presenting every possible 12-base pair sequence on an array of more than 8 million unique sequences.

According to Proteovista, resulting fluorescence intensities directly correlate to solution binding affinities for each sequence, allowing users to predict where a molecule will bind in the genome.

In the new NIH-funded project, Proteovista aims to build on its existing technology to create aptamer specificity and affinity for protein, or APT-SNAP, arrays. In the grant abstract, the company described the tool as a "high-throughput device to design, discover, and optimize high-affinity aptamers for heart disease biomarkers."

Mary Ozers, Proteovista's chief scientific officer and co-founder, told BioArray News this week that APT-SNAP arrays will display millions of unique aptamers on a single glass slide. "Nucleic acid aptamers are composed of either DNA or RNA and adopt a compact three-dimensional structure that can recognize a target, such as a cardiac biomarker," Ozers said. "We will use the APT-SNAP platform to build high-affinity aptamers for specific cardiac biomarkers found in human serum."

Part of Proteovista's proposal is to develop a methodology to synthesize high-density RNA aptamer arrays, "which we believe is a ground-breaking advancement in complexity over current RNA spotted arrays," said Ozers. She added that the company hopes to have the chips developed within the next two years.

As part of the grant, the new arrays will be used to identify biomarkers that span the cardiovascular disease spectrum from developing atherosclerosis to late-stage disease. Aptamers will be identified on the APT-SNAP array for major cardiac biomarkers as proof of principle, and identified aptamers for the cardiac biomarkers will be tested for their limit of detection in human serum.

The APT-SNAP array will also identify aptamers that recognize distinct glycosylation structures at specific residues of a biomarker, using the heart failure marker NT-proBNP as a model. To accomplish this, the company will synthesize a set of NT-proBNP proteins, each with a distinct glycosylation pattern, and iteratively design aptamers that specifically recognize the glycosylated BNP forms, according to the grant.

"Biomarkers are rarely analyzed for specific post-translational modification states, such as glycosylation, although PTMs provide key readout on protein function, localization, and signaling," said Ozers. She said that existing assays for the cardiac biomarker, NT-proBNP "do not accurately detect glycosylated NT-proBNP," although this is the predominant form of NT-proBNP in patients with heart failure and chronic kidney failure.

Because of this, she claimed the firm's platform in development will address an unmet need in cardiac medicine. "This platform can be applied to any potential cardiac markers and their glycosylation states, which will exponentially increase the pool of potential biomarkers of early cardiac disease," said Ozers.

The firm plans to develop APT-SNAP as a biomarker discovery platform, clinically correlate additional biomarkers, and develop an affordable annual point-of-care diagnostic test for hundreds of cardiac biomarkers for physician use, according to the grant abstract. The company believes the technologies will "impact the ability to diagnose heart disease accurately, allowing for better treatment options, improved patient care, and longer lifespans."

Ozers said that Proteovista aims to perform discovery for additional early-stage cardiac disease biomarkers and to partner with a diagnostic company to develop a point-of-care device for physician use and over-the counter consumer use based on its array technology.

"If a patient wants to know if they are developing heart disease, we hope to ultimately be able to devise an assay to inform them early in the process that they need to seek medical care, change their lifestyle, or make other healthy choices," she said.

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