Snap-To-It Probes

卡扣式探头

基本信息

批准号：
7501444
负责人：
Joel R Morgan
金额：
$ 36.38万
依托单位：
SYNTRIX BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7501444
关键词：
Area BRCA1 gene Binding Characteristics Chemistry Clinical Collaborations DNA DNA Probes Development Diagnostic Dissociation Environmental Engineering technology Equilibrium Exhibits Fluorescence Gel Gene Expression Glass Histidine In Situ Kinetics Label Letters Malignant Neoplasms Measures Methods Molecular Monitor Mutation Nickel Nitrilotriacetic Acid Nucleic Acid Probes Nucleic Acids Nucleotides Oligonucleotide Microarrays Oligonucleotide Probes Peptide Nucleic Acids Performance Phase Polymerase Chain Reaction Positioning Attribute Process Relative (related person)Small Business Funding Mechanisms Small Business Innovation Research Grant Solid Solutions Specificity Staging Standards of Weights and Measures Synthesis Chemistry Technology Temperature Testing Thermodynamics Tumor Suppressor Genes Universities Washington base cyanine dye density design fundamental research iminodiacetic acid improved indexing melting novel phosphoramidite programs prototype research study success tool

项目摘要

DESCRIPTION (provided by applicant): Microarrays offer the potential to profile genetic alterations in a highly multiplexed format, but have suffered from sub-optimal specificity of target capture. Array technologies which improve the specificity of target capture will be of commercial value by allowing the manufacture of arrays with superior performance characteristics. We propose to develop a novel Snap-To-It array technology that consists of arrayed PNA and DNA probes that are conformationally constrained by an intra-molecular chelate. Binding to target results in the chelate dissociation and the probe snapping to the target nucleic acid in what is an all-or-none mechanism. Consistent with previous, solution phase, thermodynamic studies using Snap-To-It probes, we hypothesize that constrained probes immobilized on an array will exhibit superior target specificity compared to unconstrained probes. The proposed chelate motifs are easily introduced into arrays using existing standard array synthesis methods with only a few additional process steps. Further, chelate binding is orthogonal to Watson-Crick pairing, and thus will not interfere with target hybridization. Phase I demonstrated feasibility of Snap-To-It probes and set the stage to move into an intensive Phase II program involving the development and testing of prototype Snap-To-It arrays for cancer analysis. DNA probes in solution and in high-throughput microarrays are invaluable tools used in areas from clinical diagnostics to fundamental research. The Snap-To-It probe technology we propose will produce microarrays with superior performance characteristics.

描述（由申请人提供）：微阵列提供了高度多重格式的遗传变化的潜力，但遭受了目标捕获的次优特异性。通过允许具有出色性能特征的阵列制造阵列，可以提高目标捕获特异性的阵列技术将具有商业价值。我们建议开发一种新型的快速阵列技术，该技术由阵列的PNA和DNA探针组成，这些探针在构象上受到分子内螯合物的构象约束。与靶向目标的结合导致螯合物解离，并在全或任何人的机制中捕获靶核酸。与使用SNAP-TO-IT探针的先前的溶液相，热力学研究一致，我们假设与无约束的探针相比，固定在阵列上的探针的约束将表现出优异的靶标特异性。使用现有的标准阵列合成方法，可以轻松地引入所提出的螯合图案，并具有一些其他过程步骤。此外，螯合结合与Watson-Crick配对是正交的，因此不会干扰目标杂交。第一阶段证明了快速到IT探针的可行性，并为进入密集的II期计划奠定了基础，该计划涉及开发和测试用于癌症分析的原型Snap-to-IT阵列。溶液和高通量微阵列中的DNA探针是从临床诊断到基础研究的领域中使用的宝贵工具。我们提出的快速探测技术将产生具有较高性能特征的微阵列。