Table of Contents
ISRN Pharmaceutics
Volume 2012, Article ID 407154, 7 pages
Research Article

Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide Derivatives and Length Optimization

1Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 21A, 106 92 Stockholm, Sweden
2GE Healthcare Bio-Sciences, Björkgatan 30, 751 84 Uppsala, Sweden
3Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA
4Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense M, Denmark
5Department of Laboratory Medicine, Karolinska Institute, Hälsovägen 7, 141 86 Huddinge, Sweden

Received 27 September 2011; Accepted 17 October 2011

Academic Editors: R. Benhida and R. Teng

Copyright © 2012 Andrés Muñoz-Alarcón et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.