Chemical Synthesis and Applications of Nucleic Acids and their Analogues

核酸及其类似物的化学合成及应用

• 批准号: RGPIN-2022-03372
• 负责人: Damha, Masad
• 金额: $ 7.5万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747838
• 关键词: Chemical; Synthesis; Applications; Nucleic; Acids

Nucleic acids are the fundamental molecules of life, carrying the genetic blueprints for all living things on Earth. Refined through billions of years of evolution, they achieve an ideal balance between complexity and elegance, a perfect marriage of form and function. As such, synthetic DNA and RNA oligonucleotides and their analogues are incredibly useful tools for molecular biology, functional genomics, and the development of oligonucleotide therapeutics. We will pursue three specific aims within this proposed NSERC Discovery Grant program, all directed to nucleic acid chemistry and biology. The short-term objective of our research is to develop methods for oligonucleotide synthesis and to design a suite of DNA/RNA analogues as tools to characterize nucleic acid structure and function. This will enable our medium-term aim of elucidating sequence-structure- function relationships for telomeric and promoter DNA quadruplexes (undoubtedly the most important classes of non-canonical DNA) and gaining a better understanding of enzymes implicated in gene regulation (CRISPR-Cas12, telomerase, etc.). This information is prerequisite to achieving our long-term goals of large-scale synthesis of improved DNA/RNA-based therapeutics capable of silencing and editing genes of interests. Hence, our research program will deliver new knowledge and new technologies to significantly advance nucleic acid chemistry and therapeutics Our scientific approach combines solution and solid-phase synthetic methods, drug discovery, spectroscopic analysis, and molecular biology techniques. These studies expose students to a wide range of topics in nucleic acid chemistry and biology research, and to strategies used for identifying candidate molecules and developing them into useful probes and/or therapeutic drugs.

核酸是生命的基本分子，携带着地球上所有生物的遗传蓝图。经过数十亿年的进化，它们在复杂性和优雅性之间达到了理想的平衡，是形式和功能的完美结合。因此，合成的DNA和RNA寡核苷酸及其类似物是分子生物学、功能基因组学和寡核苷酸疗法开发的非常有用的工具。我们将追求三个具体的目标，在这个拟议的NSERC发现补助金计划，所有针对核酸化学和生物学。我们的研究的短期目标是开发寡核苷酸合成的方法，并设计一套DNA/RNA类似物作为表征核酸结构和功能的工具。这将使我们的中期目标阐明端粒和启动子DNA四链体的序列-结构-功能关系（无疑是最重要的一类非经典DNA），并更好地了解与基因调控有关的酶（CRISPR-Cas 12，端粒酶等）。这些信息是实现我们大规模合成能够沉默和编辑感兴趣的基因的改进的基于DNA/RNA的疗法的长期目标的先决条件。因此，我们的研究计划将提供新知识和新技术，以显着推进核酸化学和治疗我们的科学方法结合了溶液和固相合成方法，药物发现，光谱分析和分子生物学技术。这些研究使学生接触到核酸化学和生物学研究的广泛主题，以及用于识别候选分子并将其开发成有用的探针和/或治疗药物的策略。