Platform for Massively Parallel Selection of Aptamer Ligands

适体配体大规模并行选择平台

• 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
• 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

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一类药物先导物和诊断配体。适体，衍生自大型组合文库的核酸配体，通常具有与抗体竞争的亲和力和特异性，但它们对于治疗和诊断应用具有许多显著的优点。不幸的是，现有的适体开发方法是低通量和繁琐的，因为DNA或RNA文库仅针对单一靶标进行筛选。该项目的重点是开发方法和工具，以允许同时对数千种蛋白质的阵列进行大的组合筛选。这种蛋白质阵列越来越多地具有高治疗和诊断价值的内容。 实现这一目标的关键是开发必要的步骤来破译哪些适体（一旦选择）对应于哪个靶标。所谓的“下一代”测序将极大地使拟议的过程加上必要的“序列标记”的方法，在这个项目中开发。一旦我们的大规模并行适体选择过程被开发出来，我们将能够在大约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表征为有前途的候选药物、诊断标签和其他研究应用，最终可能包括个性化医学。