OPTICALLY ENHANCED OLIGONUCLEOTIDES TO SCREEN FOR METABOLIC DISEASES

用于筛选代谢疾病的光学增强寡核苷酸

• 批准号: 8360021
• 负责人: ANDREA E HOLMES
• 金额: $ 4.23万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360021
• 关键词: Address; Binding; Biological Assay; Color; Complex; Development; Devices; Disease Marker; Dyes; Fluorescence; Fluorescence Spectroscopy; Fluorescent Dyes; Funding; Gel; Grant; Maps; Mass Screening; Measures; Medical; Metabolic Diseases; Methods; Molecular; Monitor; National Center for Research Resources; Nebraska; Newborn Infant; Oligonucleotides; Polymers; Principal Investigator; Property; Research; Research Infrastructure; Resources; Screening procedure; Silicates; Solid; Source; Steroids; Testing; Time; United States National Institutes of Health; Urine; aptamer; base; combinatorial; cost; cost effective; functional genomics; interest; molecular recognition; sensor; steroid metabolism

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Current screening methods for metabolic diseases are too costly, expensive, and time-consuming for broadly testing all newborns. Thus, many metabolic diseases go undetected and untreated for many years and screening is implemented only for the one most common metabolic disease. Using the proposed sol-gel supported aptamer-dye mix-and-measure assays in urine allows for cost-effective mass screening. The roposed research is dedicated to the development of new, highly selective, and sensitive molecular sensors that change color or fluorescence properties in the presence of steroid metabolites. Several steroids are disease markers for inborn metabolic diseases. We are interested in mapping three-way junctions of oligonucleotide-based binders (aptamers) to determine general principles that can be used in understanding molecular recognition of fluorescent dyes, visible dyes, steroids, and their metabolites by aptamers. The screening of aptamer-dye complexes will address an important medical need by generating cost-effective, rapid, mix-and-measure methods suitable for mass screening and monitoring of steroids or metabolites caused by faulty steroid metabolism. Organic dyes that form strong complexes with binding aptamers and metabolites will be found using a combinatorial 96-well plate approach. Reliable aptamer binding assays by UV-Vis and fluorescence spectroscopy have been established by our group. Furthermore, aptamers will be incorporated into colloidal silicate polymers for the development of handheld solid sensor devices to be used in medicinal applications. "Sol-gels" are based on solid colloidal silicates that will form a porous hard gel and will incorporate the aptamer-dye complexes within the gel, allowing for attaching the new molecular sensors into a solid support.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 代谢疾病的当前筛查方法太昂贵，昂贵且耗时，无法广泛测试所有新生儿。因此，许多代谢疾病多年来未被发现且未治疗，并且仅针对一种最常见的代谢疾病进行筛查。使用所提出的Sol-Gel支持的适体液中的尿液中的混合测定测定，可以进行具有成本效益的质量筛查。 扎根的研究致力于开发新的，高度选择性和灵敏的分子传感器，这些传感器在存在类固醇代谢物的情况下会改变颜色或荧光性能。几种类固醇是先天代谢疾病的疾病标志物。我们有兴趣映射基于寡核苷酸的粘合剂（适体）的三向连接，以确定可用于理解荧光染料，可见染料，类固醇及其代谢物的分子识别的一般原理。 适体配合物的筛选将通过产生成本效益，快速，混合度量方法来满足重要的医疗需求，适合于质量筛查和监测由类固醇代谢错误引起的类固醇或代谢产物的监测。将使用组合96孔板进近的有机染料与结合适体和代谢产物形成强配合物。我们的组已经建立了紫外线和荧光光谱法的可靠适体结合测定。 此外，适体将被合并到胶体硅酸盐聚合物中，以开发用于药用应用中的手持固体传感器设备。 “溶胶 - 凝胶”基于固体胶体硅酸盐，将形成多孔硬凝胶，并将适体型复合物掺入凝胶中，从而使新的分子传感器将新分子传感器连接到固体支持中。