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

项目摘要/摘要 标题：利用先进的基于MS的数据分析加速基因治疗和编辑非标准和 杂合核苷酸序列 本项目旨在提高可靠性，加快救生增寿发展 以寡核苷酸为基础的疗法，放大生物医学研究和教育的积极影响 在世界范围内，导致了我们对分子和细胞途径和 涉及健康和疾病生物系统的机制。高分辨质谱法直接测序 光谱分析是这些治疗药物开发和质量保证/制造过程中必不可少的分析方法，但 由于软件不足，数据分析管道中的人工干预造成了瓶颈 将这些救命疗法提供给有需要的人的过程。同样，对RNA的深入表征 而改善生物标志物鉴定所需的它们的修饰在RNA研究中受到阻碍 社区。 为了应对这些挑战，通过质谱学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。 将对MassMatrix的寡核苷酸测序引擎进行增强，以确定非标准的特征， 杂交寡核苷酸和共轭寡核苷酸。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团队之间的协作。加在一起，这些 AIMS预计将提高结果的可靠性和准确性，并显著减少 寡核苷酸表征为制药业和研究界的瓶颈。更深 理解和更好的决策将随之而来，这两者都可能对 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- 拯救和加强治疗。

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.