HIGH THROUGHPUT DNA REPAIR CAPACITY ASSAY

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One commonality amongst the human cancers is that they all contain a genetic defect which directly or indirectly results in the progression of the neoplasia. These genetic defects can arise from a number of sources, including environmental damage to DNA, metabolic damage to DNA, viral infection, or faulty genes may be inherited leading to a predisposition. The accumulation of DNA damage is thought, therefore, to be at least partially responsible for the initiation of neoplastic development. When cells are subjected to extreme environments, or when there is a deficiency in part or all of the repair system, DNA damage accumulates. This Phase I SBIR proposal outlines the development of a high throughput assay for the investigation of DNA repair capacity. The assay is based upon the immobilization of short double-stranded labeled oligonucleotide DNA sequences containing specific base modifications that serve as substrates for DNA repair. The oligonucleotides are immobilized into the wells of a multiwell microplate or alternatively painted onto the surface of a microscope slide in an array format. The assay measures changes in amount of label following exposure to cell extracts. PROPOSED COMMERCIAL APPLICATIONS: The assay provides a rapid method for screening cell or patient samples for their ability to repair specific types of DNA damage. The assay has applications in the basic research, clinical and drug discovery markets. It provides a rapid screening method for DNA repair capacity and may be a useful tool for the development of new drugs that either enhance repair (maybe useful for cancer prevention) or specifically inhibit repair (useful for preventing repair during chemotherapeutic treatments). Such an assay could also allow clinical oncologists to evaluate the effectiveness of certain treatments. Trevigen estimates the commercial potential of a DNA repair capacity assay to be over $100 million annually.