Binding-Induced DNA Assembly and Novel Applications to Ultrasensitive Detection of Proteins

结合诱导的 DNA 组装和超灵敏蛋白质检测的新应用

• 批准号: 435592-2013
• 负责人: Zhang, Hongquan
• 金额: $ 2.33万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=552812
• 关键词: Binding; Induced; DNA; Assembly; Novel

Cancer is the leading cause of morbidity and mortality in both Canadian men and women. Early detection of cancer while still localized and curable promises to reduce not only overall cancer mortality but also morbidity and economic burden. Developing tools for cancer screening based on biomarkers (indicators of biological states) represents one of the most promising approaches to identification of cancer at its early stages. Early cancer detection requires highly sensitive and specific technologies that furthermore enable rapid, reproducible, cost-effective, and high-throughput detection of biomarkers. Almost none of the available technologies for protein detection meet all of these requirements, even though proteins account for the majority of cancer biomarkers in clinical use. To fulfill the demands of protein detection for early cancer detection, I propose to develop a versatile toolbox including two types of novel homogeneous assays with complementary behaviors. The first type of assays will be developed to enable detection of as few as a hundred biomarker molecules, which is of great importance for detection of biomarkers present at ultra-low levels at early cancer stages. The second type of assays will be developed to enable detection of biomarkers at or near the site of patient care, which allows for the delivery of testing conveniently and immediately to patients. To develop these assays, I propose an attractive strategy termed binding-induced DNA assembly (BINDA). BINDA bestows some appealing features on these assays, including high sensitivity and specificity, ease of operation, and detection in a single tube. This research program will contribute to technological requirements for early cancer detection and to the basic principles of bioanalytical chemistry for homogeneous analysis.

癌症是加拿大男性和女性发病和死亡的主要原因。早期发现癌症，同时仍然是局部和可治愈的，不仅有望降低总体癌症死亡率，而且还能降低发病率和经济负担。开发基于生物标志物（生物状态指标）的癌症筛查工具是在早期阶段识别癌症的最有希望的方法之一。早期癌症检测需要高度敏感和特异性的技术，进一步实现快速、可重复、经济高效和高通量的生物标志物检测。几乎没有一种可用的蛋白质检测技术满足所有这些要求，尽管蛋白质在临床应用中占大多数癌症生物标志物。为了满足早期癌症检测中蛋白质检测的需求，我建议开发一个多功能工具箱，包括两种具有互补行为的新型同质检测方法。第一种类型的检测方法将能够检测到少至100个生物标志物分子，这对于检测癌症早期超低水平的生物标志物非常重要。将开发第二种检测方法，以便在患者护理现场或附近检测生物标志物，从而方便和立即向患者提供检测。为了开发这些检测，我提出了一种有吸引力的策略，称为结合诱导DNA组装（BINDA）。BINDA赋予这些检测方法一些吸引人的特点，包括高灵敏度和特异性，易于操作，在单管中检测。该研究项目将有助于早期癌症检测的技术要求和同质分析的生物分析化学基本原理。