Efficient inhibition of miR-155 function in vivo by peptide nucleic acids.
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.
Fabani
Martin M
MM
Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. mfabani@mrc-lmb.cam.ac.uk
Abreu-Goodger
Cei
C
Williams
Donna
D
Lyons
Paul A
PA
Torres
Adrian G
AG
Smith
Kenneth G C
KG
Enright
Anton J
AJ
Gait
Michael J
MJ
Vigorito
Elena
E
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008872:Microwaves; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism
D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger