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

项目概要/摘要 标题：加速基因治疗和编辑与先进的基于MS的数据分析，为非标准和 杂合核苷酸序列 该项目旨在提高可靠性，加快救生和增寿技术的发展。 以抗结核药物为基础的治疗方法，并扩大生物医学研究和教育的积极影响 在世界范围内，导致我们对分子和细胞途径的理解发生了质的飞跃， 健康和疾病生物系统中的机制。通过高分辨率质谱直接测序 光谱法是这些治疗剂的开发和QA/制造中的基本测定， 由于软件不足，在数据分析管道中的人工干预已经造成了 将这些拯救生命的疗法送到需要的人手中的过程。类似地，RNA的深入表征 并且在RNA研究中阻碍了它们的修饰以改善生物标志物鉴定 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的寡核苷酸测序引擎的增强将用于表征非标准， 杂合和缀合寡核苷酸。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跨团队的协作。所有这些 目标是提高结果的可靠性和准确性，并大大减少 这是制药工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，这两者都可能产生巨大的积极影响， 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， 节省和增强治疗。

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.