Platform for Massively Parallel Selection of Aptamer Ligands

适体配体大规模并行选择平台

基本信息

批准号：
8338877
负责人：
George W Jackson
金额：
$ 43.37万
依托单位：
BIOTEX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8338877
关键词：
Affinity Anisotropy Antibodies Automation Binding Bioinformatics Biological Assay Calorimetry Cells Coupled Custom DNA DNA Library Data Base Management Development Diagnostic Diversity Library Evaluation Fluorescence-Activated Cell Sorting Genetic Transcription Goals Hybrids Image Immunoglobulin Constant Region In Situ Individual Kinetics Label Libraries Ligand Binding Ligands Light Marketing Measures Medicine Methods Metric Nucleic Acids Oranges Output Paper Performance Pharmaceutical Preparations Phase Positioning Attribute Process Protein Array Protein Microchips Proteins Protocols documentation RNA RNA library Randomized Reaction Reporting Research Risk Robotics Safety Sequence Alignment Small Business Innovation Research Grant Specificity Spottings Structure Surface Plasmon Resonance Technology Testing Therapeutic Thermodynamics Time Translations Validation Western Blotting Work aptamer base combinatorial density drug candidate drug development interest next generation novel phase 1 study therapeutic protein tool

项目摘要

DESCRIPTION (provided by applicant): Aptamers have emerged as one of the most promising classes of drug leads and diagnostic ligands presently available. Aptamers, nucleic acid ligands derived from large combinatorial libraries, typically have affinities and specificities that rival antibodies, yet they have a number of significant advantages for therapeutic and diagnostic applications. Unfortunately, the existing process for aptamer development is low-throughput and tedious as DNA or RNA libraries are screened against only a single target. This project focuses on developing the methods and tools to allow large combinatorial to be screened against arrays of thousands of proteins simultaneously. Such protein arrays are increasing available with content of high therapeutic and diagnostic value. The key to achieving this is developing the necessary steps to decipher which aptamers (once selected) correspond to which target. So-called "next generation" sequencing will greatly enable the proposed process coupled with the necessary "sequence-tagging" approaches developed in this project. Once our massively parallel aptamer selection process is developed, we will be in a position to create high affinity aptamer ligands to thousands of proteins in roughly 1 week. The developed ligands can then be further characterized as promising drug candidates, diagnostic labels, and other research applications perhaps eventually including personalized medicine.

描述（由申请人提供）：适体已成为目前可用的最有前途的药物铅和诊断配体的类别之一。适体，源自大型组合文库的核酸配体，通常具有与抗体相匹配的亲和力和特异性，但它们在治疗和诊断应用方面具有许多重要的优势。不幸的是，由于DNA或RNA库仅针对单个目标筛选，因此现有的适体开发过程是低通量和乏味的。该项目着重于开发方法和工具，以同时对数千种蛋白质的数组进行筛选大型组合。这种蛋白质阵列可用于高治疗和诊断价值的含量。实现这一目标的关键是开发必要的步骤来解密适体（一旦选择）与哪个目标相对应。所谓的“下一代”测序将极大地促进所提出的过程，并在本项目中开发的必要的“序列标记”方法。一旦我们开发了大量平行的适体选择过程，我们将在大约1周内为数千种蛋白质创建高亲和力适体配体。然后，开发的配体可以进一步将其描述为有前途的候选药物，诊断标签和其他研究应用，也许最终包括个性化医学。