From Molecular Diagnostics to Therapeutics with Aptamers

从分子诊断到适体治疗

• 批准号: RGPIN-2015-05323
• 负责人: Berezovski, Maxim
• 金额: $ 2.55万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632582
• 关键词: Molecular; Diagnostics; Therapeutics; Aptamers

One of the most demanding and challenging tasks of bioanalytical chemistry and bioseparation is the replacement of animal- and hybridoma-made antibodies that have high production cost and short shelf life with artificial competitors that can be easily selected and chemically synthesized in high purity at low cost. Aptamers as “synthetic antibodies” have enormous potential. These small single-stranded DNA or RNA oligonucleotides can bind with high affinity and specificity to a variety of different targets ranging from small molecules to proteins. They are affinity ligands with significant potential to change the field of affinity probes and to replace antibodies as diagnostic and separation applications. I propose the development of three related research themes: 1) affinity purification of cells by switchable aptamers, 2) detection and imaging of rare cells by aptamers, and 3) discovery of rare cell biomarker by aptamers and mass spectrometry.

生物分析化学和生物分离最苛刻和最具挑战性的任务之一是用易于选择并以低成本高纯度化学合成的人工竞争剂替代生产成本高和保质期短的动物和杂交瘤制造的抗体。适体作为“合成抗体”具有巨大的潜力。这些小的单链 DNA 或 RNA 寡核苷酸可以以高亲和力和特异性结合从小分子到蛋白质的各种不同靶标。它们是亲和配体，具有改变亲和探针领域并取代抗体作为诊断和分离应用的巨大潜力。我建议发展三个相关的研究主题：1）通过可切换适体对细胞进行亲和纯化，2）通过适体对稀有细胞进行检测和成像，3）通过适体和质谱法发现稀有细胞生物标志物。