Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′ OMePS AON and ZM2 NP-AON Complexes in mdx Mice.
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-phosphorothi...
| Publicado en: | Journal of Biomedicine & Biotechnology Vol. 2012; pp. 1 - 9 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104297881&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104297881 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11107243 137K jtl: Journal of Biomedicine & Biotechnology issn: 11107243 maglogo: N pubinfo: dt: 2012 vid: 2012 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104297881 104297881 2011906803 NLM23091362 PMC3471065 104297881 ppf: 1 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′ OMePS AON and ZM2 NP-AON Complexes in mdx Mice. aug: au: 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 affil: Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Via Fossato di Mortara 74, 44100 Ferrara, Italy sug: subj: Drug Delivery Systems Nucleotides Administration and Dosage Muscular Dystrophy, Duchenne Drug Therapy Muscle Proteins Metabolism Animal Studies Mice Administration, Intraperitoneal Blotting, Western RNA Analysis Nanotechnology Funding Source ab: 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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