Antisense oligonucleotides (ASOs) have the ability of binding to endogenous nucleic acid targets, thereby inhibiting the gene expression. Although ASOs have great potential in the treatment of many diseases, the search for favorable toxicity profiles and distribution has been challenging and consequently impeded the widespread use of ASOs as conventional medicine. One strategy that has been employed to optimize the delivery profile of ASOs, is the functionalization of ASOs with cationic amine groups, either by direct conjugation onto the sugar, nucleobase or internucleotide linkage. The introduction of these positively charged groups has improved properties like nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has been separated into three sections, nucleobase, sugar and backbone modifications, highlighting what impact the cationic amine groups have on the ONs/ASOs physiochemical and biological properties. Finally, a concluding section has been added, summarizing the important knowledge from the three chapters, and examining the future design for ASOs.

中文翻译：

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阳离子寡核苷酸衍生物和偶联物：增强 DNA 和 RNA 靶向寡核苷酸的有利方法

反义寡核苷酸（ASO）具有与遗传核酸靶标结合的能力，从而抑制基因表达。尽管 ASO 在治疗许多疾病方面具有巨大潜力，但寻找有利的毒性特征和分布一直具有挑战性，并阻碍了 ASO 作为常规药物的广泛使用。一种已用于优化 ASO 递送特性的策略是通过直接缀合到糖、核碱基或核苷酸间键合上的阳离子胺基团对 ASO 进行功能化。这些带正电荷的基团的引入具有改进的特性，如核酸酶抗性、与核酸靶标的结合增加以及寡核苷酸 (ON) 和 ASO 的细胞摄取改善。本综述中强调的修饰是一些最流行的阳离子胺基团，它们已作为单一修饰连接到 ON/ASO 上。该综述分为三个部分，核碱基、糖和骨架修饰，重点介绍了阳离子胺基团对 ONs/ASOs 理化和生物学特性的影响。最后，增加了一个结论部分，总结了三章中的重要知识，并检查了 ASO 的未来设计。