SNAP-TO-IT PNA ARRAYS

Microarrays offer the potential to profile genetic alterations in a highly multiplexed format, but have suffered the sub-optimal specificity of target capture. Array technologies which improve the specificity of target capture will be of commercial value by allowing the manufacture of arrays with superior performance characteristics. We propose to develop a novel "Snap-To-It" array technology that consists of arrayed peptide nucleic acid (PNA) probes that are conformationally constrained by intra-molecular chelate. Binding to target results in the chelate dissociating and the PNA probe "snapping to" the target nucleic acid in what is an all-or-none mechanism. Consistent with previous thermodynamic studies, we hypothesize that the proposed constrained PNA probes will exhibit superior target specificity compared to unrestrained probes. However, in contrast to methods that utilize a DNA stem to constrain probe conformation, the proposed chelate motifs are easily introduced into arrays using our existing manufacturing platform, and in only a few process steps. Further, chelate binding is orthogonal to Watson-Crick pairing, and thus simplifies probe design by obviating the potential for unpredictable and erroneous binding between stem and target. Demonstrating feasibility will set the stage to move into an intensive Phase II program involving development and testing of a prototype Snap-To-It array for detecting mutations in the p53 tumor suppressor gene, Phase III will result in innovative Snap-To-It arrays for cancer analysis in basic, clinical, and epidemiological research markets. PROPOSED COMMERCIAL APPLICATIONS: Snap-To-It PNA arrays are intended to capture a portion of the array market served by DNA arrays. This market is estimated to be over $500 million based on aggregate revenue from companies in the market segment. Market penetration of products will be achieved through joint ventures with established corporations.