Abstract The properties of gapmer antisense oligonucleotide (ASO) flanked by deoxyribonucleic guanidine (DNG) were investigated for the potential application in antisense technology. DNG is a unique nucleotide analog which has a positively charged internucleotide guanidinium linkage instead of negatively charged phosphodiester backbone linkage. We prepared a gapmer ASO containing DNG units at both wings of the sequence and compared its properties with 2′,4′-BNA/LNA gapmer ASOs with phosphorothioate (PS) backbone. Although DNG gapmer showed no stabilizing effect on the duplex formation with target RNA, the DNG modification was found to be tolerant to exonuclease digestion. Furthermore, DNG gapmer can induce RNase H-mediated cleavage of target RNA molecule, a requisite property for the antisense strategy. Therefore, the DNG gapmer developed in this study could be an interesting and useful candidate for the development of potent ASOs.

中文翻译：

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具有脱氧核糖核酸胍 (DNG) 修饰的 gapmer 反义寡核苷酸的开发

摘要 为了在反义技术中的潜在应用，研究了侧接脱氧核糖核酸胍（DNG）的gapmer反义寡核苷酸（ASO）的性质。DNG 是一种独特的核苷酸类似物，它具有带正电荷的核苷酸间胍键，而不是带负电荷的磷酸二酯骨架键。我们在序列的两翼制备了含有 DNG 单元的 gapmer ASO，并将其特性与具有硫代磷酸酯 (PS) 骨架的 2',4'-BNA/LNA gapmer ASO 进行了比较。尽管 DNG gapmer 对与目标 RNA 的双链体形成没有稳定作用，但发现 DNG 修饰能够耐受外切核酸酶消化。此外，DNG gapmer 可以诱导 RNase H 介导的目标 RNA 分子裂解，这是反义策略的必要特性。所以，