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: 8167507
• 负责人: ANDREA E HOLMES
• 金额: $ 4.46万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167507
• 关键词: Address; Binding; Biological Assay; Color; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Devices; Disease Marker; Dyes; Fluorescence; Fluorescence Spectroscopy; Fluorescent Dyes; Funding; Gel; Grant; Institution; Maps; Mass Screening; Measures; Medical; Metabolic Diseases; Methods; Molecular; Monitor; Newborn Infant; Oligonucleotides; Polymers; Property; Research; Research Personnel; Resources; Screening procedure; Silicates; Solid; Source; Steroids; Testing; Time; United States National Institutes of Health; Urine; aptamer; base; combinatorial; cost effective; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目前的代谢性疾病筛查方法过于昂贵，昂贵且耗时，无法广泛测试所有新生儿。因此，许多代谢性疾病多年未被发现和治疗，并且仅对一种最常见的代谢性疾病进行筛查。使用所提出的溶胶-凝胶支持的核酸适体-染料混合和测量测定法在尿液中允许成本有效的大规模筛选。 该研究致力于开发新的，高选择性和灵敏的分子传感器，在类固醇代谢物存在下改变颜色或荧光特性。几种类固醇是先天性代谢疾病的疾病标志物。我们感兴趣的是映射三路路口的基于阿托伐他汀的粘合剂（适体），以确定一般原则，可用于了解分子识别的荧光染料，可见染料，类固醇，及其代谢物的适体。 适体-染料复合物的筛选将通过产生适合于大规模筛选和监测类固醇或由错误的类固醇代谢引起的代谢物的具有成本效益的、快速的、混合和测量的方法来解决重要的医学需求。使用组合96孔板方法将发现与结合适体和代谢物形成强复合物的有机染料。我们的小组已经建立了可靠的紫外-可见和荧光光谱法的适体结合测定。 此外，适体将被纳入胶体硅酸盐聚合物的手持固体传感器设备的发展，用于医疗应用。“溶胶-凝胶”基于固体胶体硅酸盐，其将形成多孔硬凝胶并将适体-染料复合物掺入凝胶内，从而允许将新的分子传感器附着到固体支持物中。