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Expert Opin Biol Ther. 2008 Jan;8(1):59-81.

MicroRNAs as targets for antisense-based therapeutics.

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University of Copenhagen, Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.


MicroRNAs (miRNAs) are a novel class of endogenous non-coding single-stranded RNAs, which regulate gene expression post-transcriptionally by base pairing with their target mRNAs. So far > 5000 miRNA entries have been registered and miRNAs have been implicated in most, if not all, central cellular processes and several diseases. As the mechanism of action for miRNA regulation of target mRNAs is mediated by Watson-Crick base pairing, antisense oligonucleotides targeting the miRNAs appear as an obvious choice to specifically inhibit miRNA function. Indeed, miRNAs can be antagonized in vivo by oligonucleotides composed of high-affinity nucleotide mimics. Lessons learned from traditional antisense strategies and small-interfering RNA approaches, that is from potent nucleotide mimics, design rules, pharmacokinetics, administration and safety issues, are likely to pave the way for future clinical trials of miRNA-antagonizing oligonucleotides.

[Indexed for MEDLINE]

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