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Multiplexed Analysis of the Epitranscriptome

表观转录组的多重分析

基本信息

批准号：
10325454
负责人：
Gudrun Stengel
金额：
$ 25.5万
依托单位：
ALIDA BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-17 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10325454
关键词：
Alternative Splicing Antibodies Antibody Affinity Architecture Bar Codes Biological Biological Assay Biological Sciences Cells Chemicals Chemistry Code Complementary DNA Complex DNA Development Diagnostic Dimensions Disease Disease Progression Drug Targeting Drug resistance Elements Enzymatic Biochemistry Exhibits Face Foundations Gene Expression Regulation Genetic Code Genetic Transcription Health Human Immunoprecipitation Individual Label Libraries Ligation Location Malignant Neoplasms Measures Medical Messenger RNA Methods Modification Molecular Oligonucleotides Pathway interactions Phase Phenotype Play Positioning Attribute Preparation Primer Extension Proteins RNA RNA immunoprecipitation sequencing Reaction Reading Reporting Research Personnel Resolution Ribosomal RNA Risk Role Sampling Science Site-Directed Mutagenesis Surface Technology Testing Transfer RNA Translation Initiation Translations Variant Virus Diseases Work analytical method antibody conjugate base commercialization density design drug development epitranscriptome epitranscriptomics experience experimental study innovation interest mRNA sequencing nanopore next generation sequencing novel strategies personalized medicine stoichiometry trafficking transcriptome tumor progression

项目摘要

Project Summary/Abstract More than 170 naturally occurring chemical modifications to RNA are known, more than 100 of which are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA, and the others. These modifications play a central role in nearly all aspects of RNA function, such as translation initiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, and regulating RNA degradation. Proteins that install, read, and remove modifications are promising drug targets of high current interest to pharma. Currently available analytical methods either do not report on sequence context or provide sequence information but at the expense of multiplexing capability. Despite these limitations, it is now known that modifications are dynamically tied to phenotypic changes in cancer progression, drug resistance, and viral infection. The focus of this application is to de-risk a new approach to RNA modification analysis capable of reading any set of RNA modifications in a multiplexed reaction, approaching single base resolution. This technology will be significant because it will provide the first method for profiling and correlating changes of multiple RNA modification types across the entire transcriptome in a given sample.

项目总结/摘要已知有超过170种天然存在的RNA化学修饰，其中100多种被发现。在所有类型的人类RNA中：mRNA，tRNA，rRNA，lncRNA，以及其他。这些修改起着核心作用在RNA功能的几乎所有方面，如翻译起始和终止、翻译保真度、替代性剪接、细胞区室之间的运输和调节RNA降解。蛋白质安装，阅读，和去除修饰是制药公司当前高度关注的有希望的药物靶点。当前可用分析方法要么不报告序列背景，要么提供序列信息，多路复用能力。尽管存在这些限制，但现在已知修改动态地绑定到癌症进展、耐药性和病毒感染中的表型变化。本申请的重点是为了降低一种新的RNA修饰分析方法的风险，该方法能够阅读RNA修饰的任何集合，多重反应，接近单碱基分辨率。这项技术将是重要的，因为它将提供了第一种用于分析和关联整个系统中多种RNA修饰类型变化的方法在给定的样品中的转录组。