Skip Navigation

Nucleic Acids Research 2006 34(2):451-461; doi:10.1093/nar/gkj455
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (509K) Freely available
Right arrow Screen PDF (518K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (10)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Kalota, A.
Right arrow Articles by Gewirtz, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kalota, A.
Right arrow Articles by Gewirtz, A. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 18 January 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{at}oxfordjournals.org

Article

2'-Deoxy-2'-fluoro-ß-D-arabinonucleic acid (2'F-ANA) modified oligonucleotides (ON) effect highly efficient, and persistent, gene silencing

A. Kalota, L. Karabon, C. R. Swider, E. Viazovkina1, M. Elzagheid1, M. J. Damha1 and A. M. Gewirtz*

University of Pennsylvania School of Medicine Philadelphia, PA, USA 1Department of Chemistry, McGill University Montreal, QC, Canada

*To whom correspondence should be addressed. Tel: +1 215 898 4499; Fax: +1 215 573 7049; Email: gewirtz{at}mail.med.upenn.edu

Received November 17, 2005. Revised January 4, 2006. Accepted January 4, 2006.

To be effective in vivo, antisense oligonucleotides (AS ON) should be nuclease resistant, form stable ON/RNA duplexes and support ribonuclease H mediated heteroduplex cleavage, all with negligible non-specific effects on cell function. We report herein that AS ONs containing a 2'-deoxy-2'-fluoro-ß-D-arabinonucleic acid (2'F-ANA) sugar modification not only meet these criteria, but have the added advantage of maintaining high intracellular concentrations for prolonged periods of time which appears to promote longer term gene silencing. To demonstrate this, we targeted the c-MYB protooncogene's mRNA in human leukemia cells with fully phosphorothioated 2'F-ANA–DNA chimeras (PS-2'FANA–DNA) and compared their gene silencing efficiency with AS ON containing unmodified nucleosides (PS-DNA). When delivered by nucleofection, chemically modified ON of both types effected a >90% knockdown of c-MYB mRNA and protein expression, but the PS-2'F-ANA–DNA were able to accomplish this at 20% of the dose of the PS-DNA, and in contrast to the PS-AS DNA, their silencing effect was still present after 4 days after a single administration. Therefore, our data demonstrate that PS-2'F-ANA–DNA chimeras are efficient gene silencing molecules, and suggest that they could have significant therapeutic potential.

Present address: L. Karabon, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
S. I. Rudnick, J. Swaminathan, M. Sumaroka, S. Liebhaber, and A. M. Gewirtz
Effects of local mRNA structure on posttranscriptional gene silencing
PNAS, September 16, 2008; 105(37): 13787 - 13792.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
X. Tang, J. Swaminathan, A. M. Gewirtz, and I. J. Dmochowski
Regulating gene expression in human leukemia cells using light-activated oligodeoxynucleotides
Nucleic Acids Res., February 2, 2008; 36(2): 559 - 569.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C. G. Peng and M. J. Damha
G-quadruplex induced stabilization by 2'-deoxy-2'-fluoro-D-arabinonucleic acids (2'F-ANA)
Nucleic Acids Res., August 1, 2007; 35(15): 4977 - 4988.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Dowler, D. Bergeron, A.-L. Tedeschi, L. Paquet, N. Ferrari, and M. J. Damha
Improvements in siRNA properties mediated by 2'-deoxy-2'-fluoro-{beta}-D-arabinonucleic acid (FANA)
Nucleic Acids Res., March 22, 2006; 34(6): 1669 - 1675.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.