Yang Yan, Yang Dongliang, Schluesener Hermann J, Zhang Zhiren
Experimental Medical Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Biomol Eng. 2007 Dec;24(6):583-92. doi: 10.1016/j.bioeng.2007.06.003. Epub 2007 Jul 5.
SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a screening technique that involves the progressive selection of highly specific ligands by repeated rounds of partition and amplification from a large combinatorial nucleic acid library. The products of the selection are called aptamers, which are short single stranded DNA or RNA molecules, binding with high affinity, attributed to their specific three-dimensional shapes, to a large variety of targets, ranging from small molecules to complex mixtures. Various improvement of the original SELEX method described in 1990 have been obtained recently, such as capillary electrophoresis SELEX, Toggle-SELEX, Tailored-SELEX, Photo-SELEX, and others. These new variants greatly shorten time of selection and improve aptamer affinity and specificity. Such aptamers have great potential as detecting and/or diagnostic reagents. Furthermore, some aptamers specifically inhibit biological functions of targeted proteins, and are considered as potent therapeutic lead structures evaluated in preclinical disease models. Recently, one aptamer has been approved by Food and Drug Administration of US for treating age-related macular degeneration. This review presents recent advances in the field of SELEX with special emphasis on applications of aptamers as analytical, diagnostic and therapeutic tools in the central nervous system.
指数富集配体系统进化技术(SELEX)是一种筛选技术,它通过从一个大型组合核酸文库中进行多轮的分离和扩增,逐步筛选出高特异性的配体。筛选的产物被称为适配体,它们是短的单链DNA或RNA分子,由于其特定的三维形状,能够以高亲和力与从小分子到复杂混合物等各种各样的靶标结合。近年来,对1990年描述的原始SELEX方法有了各种改进,如毛细管电泳SELEX、Toggle-SELEX、定制SELEX、光控SELEX等。这些新变体大大缩短了筛选时间,提高了适配体的亲和力和特异性。这类适配体作为检测和/或诊断试剂具有巨大潜力。此外,一些适配体能够特异性抑制靶蛋白的生物学功能,被视为在临床前疾病模型中评估的有效治疗先导结构。最近,一种适配体已被美国食品药品监督管理局批准用于治疗年龄相关性黄斑变性。本文综述了SELEX领域的最新进展,特别强调了适配体在中枢神经系统中作为分析、诊断和治疗工具的应用。