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- Title
Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′ OMePS AON and ZM2 NP-AON Complexes in mdx Mice.
- Authors
Bassi, Elena; Falzarano, Sofia; Fabris, Marina; Gualandi, Francesca; Merlini, Luciano; Vattemi, Gaetano; Perrone, Daniela; Marchesi, Elena; Sabatelli, Patrizia; Sparnacci, Katia; Laus, Michele; Bonaldo, Paolo; Rimessi, Paola; Braghetta, Paola; Ferlini, Alessandra
- Abstract
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 mdxmice. Our data therefore demonstrate the long-termresidual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules.
- Subjects
MUSCLE protein metabolism; RNA analysis; ANIMAL experimentation; DRUG delivery systems; DRUG administration; DUCHENNE muscular dystrophy; MICE; NANOTECHNOLOGY; NUCLEOTIDES; PERITONEUM; RESEARCH funding; WESTERN immunoblotting
- Publication
Journal of Biomedicine & Biotechnology, 2012, Vol 2012, p1
- ISSN
1110-7243
- Publication type
Article
- DOI
10.1155/2012/897076