From Molecular Diagnostics to Therapeutics with Aptamers

生物分析化学和生物分离领域最苛刻和最具挑战性的任务之一是用人工竞争对手替代动物和杂交瘤制造的抗体，这些抗体生产成本高，保质期短，可以很容易地选择和以低成本以高纯度化学合成。适配体作为“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各种不同的靶标，从小分子到蛋白质。它们是具有显著潜力的亲和配体，可以改变亲和探针领域，并取代抗体作为诊断和分离应用。我建议发展三个相关的研究主题：1)可转换适配体对细胞的亲和纯化，2)利用适配体对稀有细胞的检测和成像，以及3)利用适配体和质谱法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.