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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 897076, 8 pages
Research Article

Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

1Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Via Fossato di Mortara 74, 44100 Ferrara, Italy
2Department of Physical and Rehabilitation Medicine, Rizzoli-Sicily IOR, 90011 Bagheria, Italy
3Department of Neurological Sciences and Vision, Section of Clinical Neurology, University of Verona, 37129 Verona, Italy
4Department of Biology and Evolution, University of Ferrara, 44121 Ferrara, Italy
5IGM-CNR, Unit of Bologna, c/o IOR, 40136 Bologna, Italy
6Department of Environmental and Life Sciences INSTM, University of Eastern Piedmont, 15121 Alessandria, Italy
7Department of Histology, Microbiology, and Medical Biotechnology, University of Padua, 35121 Padua, Italy

Received 21 March 2012; Revised 25 May 2012; Accepted 14 June 2012

Academic Editor: Steve Winder

Copyright © 2012 Elena Bassi 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.


In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week) of 2 -O-methyl-phosphorothioate antisense oligoribonucleotides (AONs) adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres) were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage). In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules.