Chemical Synthesis and Applications of Oligonucleotide Analogues

寡核苷酸类似物的化学合成及应用

• 批准号: RGPIN-2017-05389
• 负责人: Hudson, Robert
• 金额: $ 3.28万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=654049
• 关键词: Chemical; Synthesis; Applications; Oligonucleotide; Analogues

My research program is concerned with the development of structurally modified oligonucleotides (DNA and RNA) and non-natural oligonucleotide mimics such as peptide nucleic acid (PNA and PMO) that: (1) expand our understanding of the chemistry, function and biology of nucleic acids; (2) will serve as sequence probes and biomolecular tools for other areas of study; and (3) may act as artificial regulators of gene expression. Another area of research is dedicated to the design, synthesis, understanding and application of contrast agents for medical imaging by magnetic resonance (MR) and positron emission tomography (PET).******Our work in the field of nucleic acid chemistry is driven by the continuing need for new biomolecular tools. Synthetic oligomers can be used as probes for diagnostics, for antisense, antigene, anti-miRNA or RNAi-based target validation studies, as aptamers and aptasensors, and in the area of functional genomics or as actual chemotherapeutics. Due to the strength in medical imaging at the Robarts Research Institute at Western University and at London Health Sciences network we have had the opportunity to build a program in the discovery of new imaging agents for serious diseases such as cancer and Alzheimer's.******This work is undertaken by a cohort of talented undergraduate, graduate and postdoctoral fellows who combine traditional solution phase small molecule synthesis with solid-phase syntheses, and key instrumental techniques. We collaborate with fellow researchers in Canada and abroad in nucleic acid chemistry and medical imaging. Thus, trainees graduate from my lab well-prepared to enter the professions in Chemistry and allied sciences as well as professional programs with an appreciation for the global nature of Science.

我的研究项目涉及结构修饰的寡核苷酸(DNA和RNA)和非天然寡核苷酸模拟物的开发，如肽核酸(PNA和PMO)：(1)扩大我们对核酸的化学、功能和生物学的理解；(2)将作为序列探针和生物分子工具用于其他研究领域；以及(3)可能作为基因表达的人工调节。另一个研究领域致力于磁共振(MR)和正电子发射断层扫描(PET)医学成像造影剂的设计、合成、理解和应用。我们在核酸化学领域的工作是由对新生物分子工具的持续需求推动的。合成的低聚物可用作诊断、反义、抗基因、抗miRNA或基于RNAi的靶向验证研究的探针，用作适配子和适配子传感器，以及在功能基因组学领域或实际的化疗药物。由于西方大学罗巴茨研究所和伦敦健康科学网络在医学成像方面的实力，我们有机会建立一个发现癌症和阿尔茨海默氏症等严重疾病的新成像剂的计划。*这项工作由一群才华横溢的本科生、研究生和博士后研究员承担，他们将传统的溶液相小分子合成与固相合成和关键仪器技术相结合。我们与加拿大和国外的研究人员在核酸化学和医学成像方面进行合作。因此，从我的实验室毕业的学员为进入化学和相关科学的专业以及专业课程做好了充分的准备，他们欣赏科学的全球本质。