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SELEX——一种用于生成高亲和力核酸配体的革命性方法。

SELEX--a (r)evolutionary method to generate high-affinity nucleic acid ligands.

作者信息

Stoltenburg Regina, Reinemann Christine, Strehlitz Beate

机构信息

UFZ, Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.

出版信息

Biomol Eng. 2007 Oct;24(4):381-403. doi: 10.1016/j.bioeng.2007.06.001. Epub 2007 Jun 16.

DOI:10.1016/j.bioeng.2007.06.001
PMID:17627883
Abstract

SELEX stands for systematic evolution of ligands by exponential enrichment. This method, described primarily in 1990 [Ellington, A.D., Szostak, J.W., 1990. In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818-822; Tuerk, C., Gold, L., 1990. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505-510] aims at the development of aptamers, which are oligonucleotides (RNA or ssDNA) binding to their target with high selectivity and sensitivity because of their three-dimensional shape. Aptamers are all new ligands with a high affinity for considerably differing molecules ranging from large targets as proteins over peptides, complex molecules to drugs and organic small molecules or even metal ions. Aptamers are widely used, including medical and pharmaceutical basic research, drug development, diagnosis, and therapy. Analytical and separation tools bearing aptamers as molecular recognition and binding elements are another big field of application. Moreover, aptamers are used for the investigation of binding phenomena in proteomics. The SELEX method was modified over the years in different ways to become more efficient and less time consuming, to reach higher affinities of the aptamers selected and for automation of the process. This review is focused on the development of aptamers by use of SELEX and gives an overview about technologies, advantages, limitations, and applications of aptamers.

摘要

SELEX代表指数富集配体的系统进化。这种方法主要在1990年被描述[埃林顿,A.D.,绍斯塔克,J.W.,1990年。体外筛选结合特定配体的RNA分子。《自然》346,818 - 822;图尔克,C.,戈尔德,L.,1990年。通过指数富集进行配体的系统进化:噬菌体T4 DNA聚合酶的RNA配体。《科学》249,505 - 510],其目的是开发适体,适体是寡核苷酸(RNA或单链DNA),由于其三维形状,能以高选择性和敏感性与其靶标结合。适体是对从蛋白质等大靶标到肽、复杂分子、药物和有机小分子甚至金属离子等差异很大的分子具有高亲和力的全新配体。适体被广泛应用,包括医学和药学基础研究、药物开发、诊断和治疗。以适体作为分子识别和结合元件的分析和分离工具是另一个大的应用领域。此外,适体用于蛋白质组学中结合现象的研究。多年来,SELEX方法以不同方式进行了改进,以变得更高效、耗时更少,使所选适体具有更高的亲和力并实现该过程的自动化。本综述聚焦于通过使用SELEX开发适体,并概述了适体的技术、优势、局限性和应用。

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