RAPID CANCER PREDISPOSITION SCREEN FOR GENE MUTATIONS

基因突变的快速癌症易感筛查

• 批准号: 2012613
• 负责人: LEONARD S BAZAR
• 金额: $ 10万
• 依托单位: TREVIGEN, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2012613
• 关键词: autoradiography; cancer risk; capillary electrophoresis; colon neoplasms; diagnosis design /evaluation; genetic disorder diagnosis; method development; neoplasm /cancer diagnosis; neoplasm /cancer genetics; nucleic acid sequence; phosphoester ligase; point mutation; solution hybridization; tissue /cell culture

TreviMed has developed a novel patent pending technology, Oscillating Cleavage Amplification Reaction (OsCAR), for the detection of point mutations in clinical samples. The entire assay will take about one hour from preparation of the DNA sample and will utilize capillary electrophoretic separation, which presently takes about two minutes. Presently, the assay detects attomole levels of target using its inherent signal amplification technology. The technology is extremely cost effective and automatable, making it attractive for large scale screening. OsCAR does not require PCR, which has been shown to be problematic for mismatch detection due to the generation of point mutations by the synthetic amplification step. In this proposal, we plan to apply Oscar to the detection of human mismatch repair enzymes implicated in hereditary nonpolyposis colon cancer (HNPCC), which is inherited in an autosomal dominant fashion resulting in colorectal cancer, and less frequently in ovary and endometrial tumors. The large gene size (73 kbp) and organization (16 exons) makes DNA sequencing and other approaches challenging, making OsCAR detection of specific high frequency mutations more practical. PROPOSED COMMERCIAL APPLICATION: This Phase I SBIR will allow feasibility testing for later development of a diagnostic system for point mutation detection of clinical samples, which is faster, more sensitive with limiting amounts of DNA and more accurate for the position of the mutation. This superior product system will have a market advantage in an over $800 million market, which is a portion of the DNA diagnostic market.

TreviMed开发了一种正在申请专利的新技术， 裂解扩增反应（OsCAR），用于检测点 临床样本中的突变。 整个检测过程大约需要 从DNA样品制备开始的24小时内，将使用毛细管 电泳分离，目前需要大约两分钟。 目前，该测定法使用其固有的特性来检测阿托摩尔水平的靶标。 信号放大技术 这项技术非常昂贵 高效和自动化，使其对大规模生产具有吸引力 筛选 OsCAR不需要PCR，这已被证明是 由于点的产生 通过合成扩增步骤进行突变。 在这个方案中，我们计划将Oscar应用于人体的检测， 与遗传性非息肉病性结肠有关的错配修复酶 癌症（HNPCC），其以常染色体显性方式遗传 导致结直肠癌，卵巢癌和 子宫内膜肿瘤 大基因大小（73 kbp）和组织（16 外显子）使得DNA测序和其他方法具有挑战性， OsCAR检测特异性高频突变更实用。 拟议的商业应用：本阶段I SBIR将允许 为以后开发诊断系统进行可行性测试， 点突变检测的临床样本，这是更快，更多 对有限数量的DNA敏感，对 突变的位置。 这种上级产品系统将具有 在超过8亿美元的市场中占据市场优势，这是 DNA诊断市场