Multiplexed Analysis of the Epitranscriptome

表观转录组的多重分析

• 批准号: 10601151
• 负责人: Gudrun Stengel
• 金额: $ 86.52万
• 依托单位: ALIDA BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-17 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10601151
• 关键词: Acceleration; Address; Aging; Alternative Splicing; Antibodies; Architecture; Automation; Bar Codes; Benchmarking; Biological; Biological Assay; Biological Sciences; Cells; Chemicals; Clinical; Clinical Trials; Code; Complementary DNA; Consumption; Coupled; Custom; DNA; Data Set; Dedications; Detection; Development; Devices; Disease; Disease Progression; Drug Targeting; Drug resistance; Elements; Environmental Risk Factor; Enzymes; Evaluation; Feedback; Funding; Genetic Code; Health; Human; Human Cell Line; Individual; Infrastructure; Inosine; Kinetics; Knowledge; Location; Malignant Neoplasms; Maps; Marketing; Measures; Messenger RNA; Methods; Modification; Molecular; Monitor; Monoclonal Antibodies; Needle biopsy procedure; Nucleotides; Pathway interactions; Performance; Phase; Phenotype; Play; Preparation; Procedures; Process; Process Measure; Property; Proteins; Protocols documentation; Publications; Publishing; Questionnaires; RNA; RNA Degradation; RNA metabolism; RNA purification; Reaction; Reader; Reading; Reagent; Reproducibility; Ribosomal RNA; Role; Running; Sampling; Science; Site; Small Business Innovation Research Grant; Specificity; Standardization; Structure; Surface; System; Technology; Testing; Therapeutic; Time; Transfer RNA; Translation Initiation; Translations; Validation; Virus Diseases; analysis pipeline; analytical method; assay development; clinical biomarkers; clinically relevant; commercial launch; commercialization; design; detection assay; detection method; detection platform; drug development; epitranscriptome; epitranscriptomics; improved; interest; multiplex assay; multiplex detection; programs; prototype; single cell analysis; symposium; trafficking; transcriptome; tumor progression; usability; 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. 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, aging, and viral infection. Alida Biosciences is developing a new commercial platform 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 low quantities of RNA may be available. Following completion of our Phase I milestones focused on creating the new multiplexed assay and proof-of-concept testing, this proposal aims to (1) complete assay development, optimizing sensitivity, specificity, and a robust and user-friendly workflow, (2) develop assay automation, and (3) perform assay validation in preparation for commercial launch. This technology will be significant because it will provide the first commercial platform capable of profiling and correlating changes of multiple RNA modification types across the entire transcriptome in a given sample.

项目摘要/摘要 表面参考组学是对RNA修饰的研究，其中包括170多种自然发生的化学物质 核苷酸的替代方案。在所有类型的人RNA中发现了60多个：mRNA，tRNA，rRNA，lncRNA， 还有其他。这些修改是动态的。它们的全球发展变化以及在 疾病进展。它们由作者酶安装，由读取器蛋白读取并由Eraser删除 酶，它们具有改变RNA结构和动力学的内在能力。它们影响翻译 引发和终止，翻译保真度，替代剪接，室内室之间的贩运以及 调节RNA降解。 RNA读取器，作家和橡皮蛋白是高电流的有前途的药物靶标 Pharma的兴趣。当前可用的分析方法要么不报告序列上下文或提供 序列信息，但以多重功能为代价。尽管有这些限制，但现在已知 这些修饰与癌症进展，耐药性，衰老和 病毒感染。 Alida Biosciences正在开发一个新的商业平台来检测，识别和映射 多重且具有高灵敏度的RNA修饰 - 适用于临床样品（例如，针头活检， FFPE样品）可能可获得低量的RNA。完成我们的I阶段里程碑之后 该建议旨在创建新的多重分析和概念概念证明测试，旨在（1）完成 测定开发，优化敏感性，特异性以及强大且用户友好的工作流程，（2）开发测定法 自动化和（3）在准备商业发布时执行测定验证。这项技术将是 意义重大，因为它将提供第一个能够分析和关联的商业平台 给定样品中整个转录组的多种RNA修饰类型。