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PMID: 20223773 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Efficient inhibition of miR-155 function in vivo by peptide nucleic acids.

Nucleic acids research ·Vol. 38 ·No. 13 ·2010-07-00 ·Pages 4466-75

Fabani MM, Abreu-Goodger C, Williams D, Lyons PA, Torres AG, Smith KG, Enright AJ, Gait MJ, Vigorito E

Abstract

MicroRNAs (miRNAs) play an important role in diverse physiological processes and are potential therapeutic agents. Synthetic oligonucleotides (ONs) of different chemistries have proven successful for blocking miRNA expression. However, their specificity and efficiency have not been fully evaluated. Here, we show that peptide nucleic acids (PNAs) efficiently block a key inducible miRNA expressed in the haematopoietic system, miR-155, in cultured B cells as well as in mice. Remarkably, miR-155 inhibition by PNA in primary B cells was achieved in the absence of any transfection agent. In mice, the high efficiency of the treatment was demonstrated by a strong overlap in global gene expression between B cells isolated from anti-miR-155 PNA-treated and miR-155-deficient mice. Interestingly, PNA also induced additional changes in gene expression. Our analysis provides a useful platform to aid the design of efficient and specific anti-miRNA ONs for in vivo use.

MeSH Terms
Animals B-Lymphocytes/metabolism Binding Sites Cells, Cultured Gene Expression Profiling Gene Expression Regulation Mice Mice, Inbred C57BL Mice, Knockout MicroRNAs/antagonists & inhibitors,genetics,metabolism Microwaves Peptide Nucleic Acids/chemical synthesis RNA, Messenger/chemistry,metabolism
Chemicals
MicroRNAs Mirn155 microRNA, mouse Peptide Nucleic Acids RNA, Messenger
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Fabani Martin M
Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. [email protected]
Abreu-Goodger Cei
Williams Donna
Lyons Paul A
Torres Adrian G
Smith Kenneth G C
Enright Anton J
Gait Michael J
Vigorito Elena
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkq160
Email
[email protected]
Published
2010-07-00
Epub
2010-00-11
Pages
4466-75
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2910044
Subset
IM
Grants
Medical Research Council · G0700287 · United Kingdom
Medical Research Council · MC_U105178803 · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
External Links
PubMed source DOI: 10.1093/nar/gkq160 PMC Full Text View journal details
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