Advances in SELEX and application of aptamers in the central nervous system

Yan Yang , Dongliang Yang , Hermann J. Schluesener , Zhiren Zhang
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引用次数: 78

Abstract

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.

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SELEX及其适配体在中枢神经系统中的应用研究进展
SELEX (Systematic Evolution of Ligands by Exponential Enrichment)是一种筛选技术,通过从大型组合核酸文库中反复分割和扩增,逐步选择高度特异性的配体。这种选择的产物被称为适体,它们是短的单链DNA或RNA分子,由于其特定的三维形状,以高亲和力结合到各种各样的靶标,从小分子到复杂的混合物。对1990年描述的原始SELEX方法进行了各种改进,例如毛细管电泳SELEX, Toggle-SELEX, Tailored-SELEX, Photo-SELEX等。这些新变异大大缩短了选择时间,提高了适体的亲和力和特异性。这种适体作为检测和/或诊断试剂具有很大的潜力。此外,一些适体特异性抑制目标蛋白的生物学功能,并被认为是临床前疾病模型中评估的有效治疗先导结构。最近,一种适体被美国食品和药物管理局批准用于治疗老年性黄斑变性。本文综述了SELEX领域的最新进展,重点介绍了适体在中枢神经系统分析、诊断和治疗方面的应用。
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