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G-四链体形成适体的特性、应用及展望。

G-Quadruplex-Forming Aptamers-Characteristics, Applications, and Perspectives.

机构信息

Department of Nucleic Acids Bioengineering, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.

出版信息

Molecules. 2019 Oct 21;24(20):3781. doi: 10.3390/molecules24203781.

Abstract

G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.

摘要

G-四链体构成了一类独特的核酸结构,由 DNA 或 RNA 型的富含 G 的寡核苷酸组成。根据其化学性质、环的长度以及在序列或结构中的定位,分子的复杂性,G-四链体是高度多态的结构,表现出各种折叠拓扑结构。它们可能存在于人类基因组中,被认为在调节多种生物学过程(如复制、转录和翻译)中发挥关键作用。因此,天然 G-四链体结构成为疾病治疗的有前途的靶点。配体系统进化的指数富集(SELEX)技术的快速发展提供了许多富含 G 的适体,揭示了 G-四链体结构作为一种有前途的分子工具,针对各种具有生物学重要性的配体的潜力。由于其高稳定性、增加的细胞摄取、易于化学修饰、较小的生产成本和方便的储存,富含 G 的适体成为抗体的有趣治疗和诊断替代品。在这篇综述中,我们描述了基于 G-四链体的适体的最新进展,重点关注了这一特殊类核酸结构的治疗和诊断潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c2/6832456/538bb9a11753/molecules-24-03781-g001.jpg

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