Rapid NGS Method for Mapping of the Epitranscriptome

表观转录组图谱快速 NGS 方法

• 批准号: 10484653
• 负责人: Gudrun Stengel
• 金额: $ 25.95万
• 依托单位: ALIDA BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2022-12-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484653
• 关键词: Address; Alternative Splicing; Antibodies; Bar Codes; Benchmarking; Binding; Biological; Biological Assay; Biological Sciences; Cells; Chemicals; Clinical; Code; DNA; Data Set; Detection; Development; Disease; Disease Progression; Drug Targeting; Drug resistance; Elements; Enzymes; Exhibits; Funding; Genetic Code; Genetic Transcription; Grant; Health; Heteroduplex DNA; Human; Impairment; Inosine; Libraries; Malignant Neoplasms; Measures; Messenger RNA; Methods; Modeling; Modification; Needle biopsy procedure; Nucleotides; Oligonucleotides; Pathway interactions; Performance; Phase; Phenotype; Play; Positioning Attribute; Preparation; Proteins; Protocols documentation; Pseudouridine; Publishing; RNA; RNA Binding; RNA Degradation; RNA library; Reader; Reading; Reporting; Resolution; Ribosomal RNA; Role; Sampling; Science; Specificity; Structure; Technology; Testing; Time; Tn5 transposase; Transfer RNA; Translation Initiation; Translations; Transposase; Virus Diseases; Work; analytical method; base; commercialization; density; drug development; epitranscriptome; epitranscriptomics; interest; mRNA sequencing; molecular recognition; next generation sequencing; novel strategies; preservation; trafficking; transcriptome; transcriptome sequencing; tumor progression; user-friendly

Project Summary/Abstract Epitranscriptomics is the study of RNA modifications, which include more than 170 naturally occurring chemical alternations to the nucleotides. More than 60 are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA, and the others. These modifications are dynamic; their global quantities change in development and during disease progression. They are installed by writer enzymes, read by reader proteins and removed by eraser enzymes, and they have an intrinsic capacity to alter RNA structure and dynamics. They influence translation initiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, and regulate RNA degradation. RNA reader, writer and eraser proteins are promising drug targets of high current interest to pharma. In this project, we will test and validate a new approach to detecting, identifying, and mapping RNA modifications in a multiplex and with high sensitivity—suitable for clinical samples (e.g. needle biopsies, FFPE samples) in which only sub-nanogram quantities of RNA may be available. This technology will be significant because it will provide the first commercial method for profiling and correlating changes of multiple RNA modification types across the entire transcriptome using low sample input.

项目总结/摘要 表位转录组学是RNA修饰的研究，其中包括170多种天然存在的化学修饰。 对核苷酸的改变。在人类所有类型的RNA中发现了60多种：mRNA，tRNA，rRNA，lncRNA， 还有其他人这些修改是动态的;它们的整体数量在发展和期间发生变化 疾病进展。它们由写入酶安装，由读取蛋白读取，并由擦除器移除 它们具有改变RNA结构和动力学的内在能力。影响翻译 起始和终止、翻译保真度、可变剪接、细胞区室之间的运输，以及 调节RNA降解。RNA阅读器、写入器和擦除器蛋白是一种很有前途的高电流药物靶点 对制药感兴趣。在这个项目中，我们将测试和验证一种新的方法来检测，识别和映射 多重和高灵敏度的RNA修饰-适用于临床样品（例如，针穿刺活检， FFPE样品），其中仅可获得亚纳克量的RNA。这项技术将 重要的是，它将提供第一个商业方法来分析和关联多个 使用低样本输入跨整个转录组的RNA修饰类型。