Institut Pasteur, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France.
Department of Chemistry, McGill University, 801 Rue Sherbrooke Street West, Montréal, H3A0B8, Canada.
Chem Soc Rev. 2021 Apr 26;50(8):5126-5164. doi: 10.1039/d0cs01430c.
While Nature harnesses RNA and DNA to store, read and write genetic information, the inherent programmability, synthetic accessibility and wide functionality of these nucleic acids make them attractive tools for use in a vast array of applications. In medicine, antisense oligonucleotides (ASOs), siRNAs, and therapeutic aptamers are explored as potent targeted treatment and diagnostic modalities, while in the technological field oligonucleotides have found use in new materials, catalysis, and data storage. The use of natural oligonucleotides limits the possible chemical functionality of resulting technologies while inherent shortcomings, such as susceptibility to nuclease degradation, provide obstacles to their application. Modified oligonucleotides, at the level of the nucleobase, sugar and/or phosphate backbone, are widely used to overcome these limitations. This review provides the reader with an overview of non-native modifications and the challenges faced in the design, synthesis, application and outlook of novel modified oligonucleotides.
尽管自然界利用 RNA 和 DNA 来存储、读取和写入遗传信息，但这些核酸具有固有的可编程性、合成可及性和广泛的功能，这使得它们成为在各种应用中使用的有吸引力的工具。在医学领域，反义寡核苷酸 (ASO)、siRNA 和治疗性适体被探索作为有效的靶向治疗和诊断方式，而在技术领域，寡核苷酸已在新材料、催化和数据存储中得到应用。天然寡核苷酸的使用限制了由此产生的技术的可能化学功能，而固有缺陷，如易受核酸酶降解的影响，为它们的应用提供了障碍。修饰的寡核苷酸，在碱基、糖和/或磷酸骨架的水平上，被广泛用于克服这些限制。本文综述了非天然修饰物以及在新型修饰寡核苷酸的设计、合成、应用和前景方面面临的挑战。
