A novel instrument for high efficiency extraction of circulating nucleic acids

一种高效提取循环核酸的新型仪器

• 批准号: 7580979
• 负责人: ANDRE MARZIALI
• 金额: $ 13.53万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-07 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7580979
• 关键词: Acrylamides; Applications Grants; Automation; Award; Biological Markers; Biotechnology; Blood Stains; Body Fluids; Cells; Clinical; Collection; Communities; Complex; DNA; DNA Markers; DNA Sequence; Detection; Development; Feces; Forensic Medicine; Future; Gel; Genomics; Human; Licensing; Link; Malignant Neoplasms; Metagenomics; Methods; Modification; Mutation; Non-Invasive Cancer Detection; Nucleic Acids; Oncogene Activation; Performance; Petroleum; Process; Recovery; Research; Risk; Sampling; Science; Sepharose; Serum; Signal Transduction; Silicon Dioxide; Site; Soil; Specificity; Tars; Technology; Testing; Urine; Validation; Work; abstracting; base; commercialization; cost; electric field; infancy; innovation; instrument; microchip; neoplastic cell; novel; tool; tumor

DESCRIPTION (provided by applicant): Circulating nucleic acids from dying tumor cells may yield an early indication of cancer if they could be detected at sufficiently low abundance in body fluids in the presence of background DNA from healthy cells as well as contaminants inherent to blood serum, urine, and stool samples. Methods capable of enriching for small quantities of partially intact tumor DNA from body fluids while rejecting contaminants and background DNA from healthy cells would be a great advantage. This would be particularly true, if the DNA could be enriched for sequence mutations that signal oncogene activation or other tumor related sequence signatures. We have developed a method of DNA concentration and extraction (SCODA) that, in its simplest form, promises to increase the amount and purity of DNA extracted from body fluids, while reducing the amount of processing steps and cost. SCODA will allow facile extraction of nucleic acid biomarkers from samples such as urine, stool, or blood serum for non-invasive cancer detection, and for genomic studies of cancer. SCODA provides a means for high efficiency concentration of low abundance DNA with a high degree of contaminant rejection. Applications of this technology to forensics and genomics research are being commercialized, and its value has been proven in both fields. We aim to apply SCODA technology to extraction of circulating DNA from body fluids ranging from blood serum to stool. We expect that its outstanding efficiency and rejection of contaminants, as proven in our forensics work, will yield benefits in biomarker extractions. Furthermore, we plan to make modifications to SCODA that will allow enrichment for specific low abundance DNA sequences. This will be done by altering the concentration mechanism, such that only DNA fragments containing specific sequences relating to tumor cells will be concentrated. This promises to provide a pre-concentration tool that would enable exceptionally sensitive detection of tumor DNA biomarkers in body fluids.

描述（由申请人提供）：如果在健康细胞的背景DNA以及血清、尿液和粪便样本中固有的污染物存在的情况下，体液中能够检测到足够低丰度的来自垂死肿瘤细胞的循环核酸，则可能产生癌症的早期指示。能够从体液中富集少量部分完整的肿瘤DNA，同时排斥来自健康细胞的污染物和背景DNA的方法将是一个巨大的优势。如果DNA能够富集致癌基因激活或其他肿瘤相关序列特征的序列突变，这将是特别正确的。