Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153, Japan.
Biochem Biophys Res Commun. 2012 Oct 5;426(4):571-7. doi: 10.1016/j.bbrc.2012.08.128. Epub 2012 Sep 7.
Short interference RNA (siRNA) is a powerful tool for suppressing gene expression in mammalian cells. In this study, we focused on the development of siRNAs conjugated with aromatic compounds in order to improve the potency of RNAi and thus to overcome several problems with siRNAs, such as cellular delivery and nuclease stability. The siRNAs conjugated with phenyl, hydroxyphenyl, naphthyl, and pyrenyl derivatives showed strong resistance to nuclease degradation, and were thermodynamically stable compared with unmodified siRNA. A high level of membrane permeability in HeLa cells was also observed. Moreover, these siRNAs exhibited enhanced RNAi efficacy, which exceeded that of locked nucleic acid (LNA)-modified siRNAs, against exogenous Renilla luciferase in HeLa cells. In particular, abundant cytoplasmic localization and strong gene-silencing efficacy were found in the siRNAs conjugated with phenyl and hydroxyphenyl derivatives. The novel siRNAs conjugated with aromatic compounds are promising candidates for a new generation of modified siRNAs that can solve many of the problems associated with RNAi technology.
短干扰 RNA（siRNA）是一种在哺乳动物细胞中抑制基因表达的强大工具。在这项研究中，我们专注于将芳香族化合物与 siRNA 连接，以提高 RNAi 的效力，从而克服 siRNA 的一些问题，如细胞递送和核酸酶稳定性。与苯、羟基苯、萘基和并苯基衍生物连接的 siRNA 对核酸酶降解具有很强的抗性，与未修饰的 siRNA 相比热力学稳定性更高。我们还观察到它们在 HeLa 细胞中具有很高的膜通透性。此外，与修饰后的锁核酸（LNA）相比，这些 siRNA 对 HeLa 细胞中外源 Renilla 荧光素酶的 RNAi 效果显著增强。特别是，与苯和羟基苯衍生物连接的 siRNA 表现出丰富的细胞质定位和强烈的基因沉默效果。这些连接了芳香族化合物的新型 siRNA 是新一代修饰 siRNA 的有前途的候选物，它们可以解决 RNAi 技术相关的许多问题。
