Institute for Virology, Campus Benjamin Franklin, Charité-University Medicine, Berlin, Germany.
FEBS Lett. 2010 Feb 5;584(3):591-8. doi: 10.1016/j.febslet.2009.12.007. Epub 2010 Jan 13.
This study describes the first application of unlocked nucleic acid (UNA)-modified small interfering RNAs (siRNAs) directed against a medically relevant target, the coxsackievirus B3. We systematically analyzed the impact of different siRNA modification patterns and observed good compatibility of the introduction of UNA with the maintenance of high antiviral activity. Additionally, the polarity of an siRNA was successfully reversed by modulating the relative stability of the termini with locked nucleic acid (LNA) and UNA as shown in a reporter assay. The potency of the reversed siRNA against the full-length target was, however, too low to inhibit the infectious virus. Altogether, combined modification of siRNAs with LNA und UNA provides a promising approach to alter and improve properties of an siRNA.
本研究描述了首例针对医学相关靶点——柯萨奇病毒 B3 的无锁定核酸（UNA）修饰的小干扰 RNA（siRNA）的应用。我们系统地分析了不同 siRNA 修饰模式的影响，并观察到 UNA 的引入与维持高抗病毒活性之间具有良好的兼容性。此外，正如在报告基因检测中所显示的，通过调节锁核酸（LNA）和 UNA 末端的相对稳定性，可以成功地反转 siRNA 的极性。然而，反转的 siRNA 对全长靶标几乎没有抑制活性，因而无法抑制感染性病毒。总的来说，LNA 和 UNA 联合修饰 siRNA 为改变和改善 siRNA 的特性提供了一种很有前途的方法。
