Hall Allison H S, Wan Jing, Spesock April, Sergueeva Zinaida, Shaw Barbara Ramsay, Alexander Kenneth A
Department of Molecular Genetics and Microbiology, Box 3020, Duke University Medical Center, Durham, NC 27710, USA.
Nucleic Acids Res. 2006 May 22;34(9):2773-81. doi: 10.1093/nar/gkl339. Print 2006.
In RNA interference (RNAi), double-stranded short interfering RNA (ds-siRNA) inhibits expression from complementary mRNAs. Recently, it was demonstrated that short, single-stranded antisense RNA (ss-siRNA) can also induce RNAi. While ss-siRNA may offer several advantages in both clinical and research applications, its overall poor activity compared with ds-siRNA has prevented its widespread use. In contrast to the poor gene silencing activity of native ss-siRNA, we found that the silencing activity of boranophosphate-modified ss-siRNA is comparable with that of unmodified ds-siRNA. Boranophosphate ss-siRNA has excellent maximum silencing activity and is highly effective at low concentrations. The silencing activity of boranophosphate ss-siRNA is also durable, with significant silencing up to 1 week after transfection. Thus, we have demonstrated that boranophosphate-modified ss-siRNA can silence gene expression as well as native ds-siRNA, suggesting that boranophosphate-modified ss-siRNAs should be investigated as a potential new class of therapeutic agents.
在RNA干扰（RNAi）中，双链短干扰RNA（ds-siRNA）可抑制互补mRNA的表达。最近有研究表明，短的单链反义RNA（ss-siRNA）也能诱导RNAi。虽然ss-siRNA在临床和研究应用中可能具有若干优势，但其与ds-siRNA相比整体活性较差，这阻碍了它的广泛应用。与天然ss-siRNA较差的基因沉默活性相反，我们发现硼磷酸修饰的ss-siRNA的沉默活性与未修饰的ds-siRNA相当。硼磷酸ss-siRNA具有出色的最大沉默活性，在低浓度下也非常有效。硼磷酸ss-siRNA的沉默活性也很持久，转染后长达1周仍有显著的沉默效果。因此，我们已经证明硼磷酸修饰的ss-siRNA能够像天然ds-siRNA一样沉默基因表达，这表明硼磷酸修饰的ss-siRNAs应作为一类潜在的新型治疗药物进行研究。
