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Technology
Isoforms have largely been ignored for clinical purposes because they have historically been hard to differentiate, identify and characterize, and there was no cost-effective assay format to facilitate clinical use of the isoform information. Molecular diagnostics address just 8-10% (SNPs and splice variants) of potential protein isoforms. Target Discovery is a pioneer in the use of hypothesis-driven methods for protein isoform biomarker discovery and validation, and clinical proteomic assays. Until recently, hypothesis-free global proteomic methods have most often been employed to discover isoform information for clinical purposes. However, global proteomic methods have proven to be too expensive and not robust enough for clinical use. Furthermore, they have failed to detect many known biomarkers because of intrinsic dynamic range and sample complexity issues. Our hypothesis-driven methods get around these intrinsic limitations.
Our clinical Isonostic™ assays couple the affinity capture step of traditional immunodiagnostics with down stream separation of all the isoforms by TDI's proprietary capillary electrophoresis process. Regulatory compliant confirmation of the specific isoforms present is accomplished from the retention time in the electrophoretic separation. The amounts of each isoform present in the sample are determined from the peak areas in the electropherogram.
Our isoform biomarker discovery and validation platform is also based on affinity enrichment of specific parent proteins from the patient sample. Our proprietary mass defect technology allows us to rapidly identify and characterize the captured protein isoforms from each other and quantify any isoform differences between paired (disease and control) patient samples.