High potency silencing by single-stranded boranophosphate siRNA.
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.
Hall
Allison H S
AH
Department of Molecular Genetics and Microbiology, Box 3020, Duke University Medical Center, Durham, NC 27710, USA.
Wan
Jing
J
Spesock
April
A
Sergueeva
Zinaida
Z
Shaw
Barbara Ramsay
BR
Alexander
Kenneth A
KA
D060565:Argonaute Proteins; D001880:Boranes / Q000737:chemistry*; D015852:Eukaryotic Initiation Factor-2; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D010448:Peptide Initiation Factors / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001880:Boranes; D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D010710:Phosphates; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C510710:boranophosphate; D012260:Ribonucleases