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Nucleic Acids Research 2006 34(9):2773-2781; doi:10.1093/nar/gkl339
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Published online 22 May 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

High potency silencing by single-stranded boranophosphate siRNA

Allison H. S. Hall1, Jing Wan2, April Spesock1, Zinaida Sergueeva2, Barbara Ramsay Shaw2 and Kenneth A. Alexander1,3,*

1 Department of Molecular Genetics and Microbiology Box 3020 Duke University Medical Center Durham, NC 27710, USA 2 Department of Chemistry Box 90354 Duke University Durham, NC 27708, USA 3 Department of Pediatrics, Section of Pediatric Infectious Diseases, The University of Chicago 5841 S. Maryland Ave., MC 6054, Chicago, IL, 60637, USA

*To whom correspondence should be addressed. Tel: 1 773 834 2711; Fax: 1 773 702 1196; Email: kalexander{at}uchicago.edu

Received January 30, 2006. Revised February 15, 2006. Accepted April 17, 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.


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