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.

项目摘要 /摘要 标题：通过基于高级MS的数据分析的非标准和编辑，用于非标准和 杂化核苷酸序列 该项目旨在提高可靠性并加快挽救生命和生命的发展 基于寡核苷酸的治疗并扩大生物医学研究和教育的积极影响 全球，导致我们对分子和细胞途径的理解以及 涉及健康和疾病生物系统的机制。通过高分辨率质量进行直接测序 光谱法是这些治疗剂的开发和质量/制造的重要评估，但是 由于软件不足而导致的数据分析管道中的手动干预已导致瓶颈 将这些挽救生命疗法的过程给有需要的人。同样，RNA的深入表征 RNA研究阻碍了他们改善生物标志识别所需的修改 社区。 为了应对这些挑战，通过质谱法对寡核苷酸的半自动直接测序将 可以在Massmatrix的高通量企业云平台（MMCloud）上实施并交付。 将对Massmatrix的寡核苷酸测序引擎进行增强，以表征非标准， 杂化和共轭寡核苷酸。关于MMCloud的统一数据存储库将启用分析比较， 知识捕获和管理，以及在研究团队内部和跨研究团队的协作。在一起，这些 目的有望提高结果的可靠性和准确性，并显着降低 制药行业和研究界的寡核苷酸表征瓶颈。更深 理解和更好的决策将随之而来，两者都对 下游过程和资源部署，包括改善药物安全，效率和寿命的可用性 - 节省和增强治疗。