From Molecular Diagnostics to Therapeutics with Aptamers

生物分析化学和生物分离的最高要求和最具挑战性的任务之一是用人工竞争物替代具有高生产成本和短保质期的动物和杂交瘤制备的抗体，所述人工竞争物可以容易地选择并以低成本以高纯度化学合成。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到从小分子到蛋白质的各种不同的靶标。它们是亲和配体，具有改变亲和探针领域和取代抗体作为诊断和分离应用的显著潜力。我提出了三个相关的研究主题的发展：1）通过可转换适体进行细胞亲和纯化，2）通过适体检测和成像稀有细胞，3）通过适体和质谱发现稀有细胞生物标志物。

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.