Accelerating Gene Therapy and Editing with Advanced MS-Based Data Analysis for Nonstandard and Hybrid Nucleotide Sequences

通过基于 MS 的高级数据分析加速非标准和混合核苷酸序列的基因治疗和编辑

• 批准号: 10699241
• 负责人: George Hall Johnson
• 金额: $ 86.06万
• 依托单位: MASSMATRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-05 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699241
• 关键词: Acceleration; Address; Adherence; Algorithms; Base Sequence; Biological Assay; Biological Sciences; Biomedical Research; Client; Collaborations; Communities; Computer software; DNA; Data; Data Analyses; Data Element; Data Science; Decision Making; Development; Disease; Disparate; Drug Industry; Education; Feedback; Future; Genes; Grant; Growth; Hybrids; Industry; Intervention; Ions; Knowledge; Life; Lipids; Machine Learning; Manuals; Marketing; Mass Spectrum Analysis; Methods; Modeling; Modernization; Modification; Molecular; Monitor; Mutation; Mutation Analysis; Occupations; Oligonucleotides; Pathway interactions; Peptides; Phase; Principal Component Analysis; Process; Quality Control; RNA; Reliability of Results; Reproducibility; Research; Resolution; Resource Allocation; Resources; Scientist; Sequence Alignment; Specific qualifier value; Speed; Standardization; System; Testing; Therapeutic; Update; Vendor; Visualization; application programming interface; base; biological systems; biomarker identification; blind; cloud platform; commercialization; data access; data analysis pipeline; data integration; data management; data repository; data sharing; data visualization; design; experience; flexibility; gene therapy; improved; manufacture; medication safety; member; next generation sequencing; novel; prototype; quality assurance; quantum; science education; sugar; tandem mass spectrometry; transcriptome sequencing; web portal; web services

PROJECT SUMMARY / ABSTRACT Title: Accelerating Gene Therapy and Editing with Advanced MS-Based Data Analysis for Nonstandard and Hybrid Nucleotide Sequences This project seeks to improve reliability and speed up the development of life-saving and life-enhancing oligonucleotide-based therapeutics and magnify the positive impact of biomedical research and education worldwide, leading to a quantum leap in our understanding of the molecular and cellular pathways and mechanisms involved in healthy and diseased biological systems. Direct sequencing via high-resolution mass spectrometry is an essential assay in the development and QA/ manufacturing of these therapeutics but manual intervention in the data analysis pipeline due to inadequate software has caused a bottleneck in the process of getting these life-saving therapeutics to those in need. Similarly, in-depth characterization of RNA and their modifications needed for improving biomarker identification is hindered in the RNA research community. To address these challenges, semi-automated direct sequencing of oligonucleotides by mass spectrometry will be implemented and delivered on MassMatrix’s high-throughput, enterprise cloud platform (mmCloud). Enhancements to MassMatrix’s oligonucleotide sequencing engine will be made for characterizing nonstandard, hybrid and conjugate oligonucleotides. A unified data repository on mmCloud will enable assay comparisons, knowledge capture and management, and collaboration within and across research teams. Together, these aims are expected to improve the reliability and accuracy of results as well as to significantly reduce the oligonucleotide characterization bottleneck for the pharmaceutical industry and the research community. Deeper understanding and better decision making will follow, both having a potentially dramatic positive impact on downstream processes and resource deployment, including improved drug safety, efficacy and availability of life- saving and enhancing therapeutics.

项目概要/摘要 标题：通过基于 MS 的高级数据分析加速非标准和基因治疗和编辑 杂合核苷酸序列 该项目旨在提高可靠性并加速救生和增强生命的发展 基于寡核苷酸的疗法并放大生物医学研究和教育的积极影响 全球范围内，导致我们对分子和细胞途径的理解发生了质的飞跃 通过高分辨率质量直接测序涉及健康和患病生物系统的机制。 光谱测定是这些疗法的开发和质量保证/制造中的重要测定方法，但是 由于软件不足，对数据分析流程的人工干预造成了瓶颈 为有需要的人提供这些挽救生命的疗法的过程，同样是对 RNA 的深入表征。 改进生物标志物识别所需的修饰在 RNA 研究中受到阻碍 社区。 为了应对这些挑战，通过质谱法对寡核苷酸进行半自动直接测序将 在 MassMatrix 的高吞吐量企业云平台 (mmCloud) 上实施和交付。 MassMatrix 寡核苷酸测序引擎的增强将用于表征非标准、 mmCloud 上的统一数据存储库将实现分析比较、 知识获取和管理，以及研究团队内部和之间的协作。 预计目标是提高结果的可靠性和准确性，并显着减少 制药行业和研究界的寡核苷酸表征瓶颈。 随之而来的是理解和更好的决策，两者都会对以下方面产生潜在的巨大积极影响： 下游流程和资源部署，包括提高药物安全性、有效性和生命可用性 节省和治疗的增强。