HIGH THROUGHPUT DNA REPAIR CAPACITY ASSAY

人类癌症的一个共同点是它们都含有直接或间接导致瘤形成进展的遗传缺陷。这些遗传缺陷可以由许多来源引起，包括环境对DNA的损伤，对DNA的代谢损伤，病毒感染，或者可能遗传导致易感性的缺陷基因。因此，DNA损伤的积累被认为至少是肿瘤发生的部分原因。当细胞处于极端环境中，或者部分或全部修复系统存在缺陷时，DNA损伤就会累积。该I期SBIR提案概述了用于研究DNA修复能力的高通量测定的开发。该测定法基于固定化含有特定碱基修饰的短双链标记寡核苷酸DNA序列，这些碱基修饰可作为DNA修复的底物。将寡核苷酸固定在多孔微孔板的威尔斯孔中，或者以阵列形式涂在显微镜载玻片的表面上。该试验测量暴露于细胞提取物后标记物量的变化。拟议的商业应用：该检测提供了一种快速筛选细胞或患者样本修复特定类型DNA损伤的能力的方法。该分析在基础研究、临床和药物发现市场中具有应用。它提供了一种快速筛选DNA修复能力的方法，并可能是一个有用的工具，用于开发新的药物，无论是增强修复（可能有助于癌症预防）或特异性抑制修复（用于防止修复化疗治疗期间）。这样的分析也可以让临床肿瘤学家评估某些治疗的有效性。Trevigen估计DNA修复能力测定的商业潜力每年超过1亿美元。

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.