Your browser doesn't support javascript.
loading
Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles.
Peccate, Cécile; Mollard, Amédée; Le Hir, Maëva; Julien, Laura; McClorey, Graham; Jarmin, Susan; Le Heron, Anita; Dickson, George; Benkhelifa-Ziyyat, Sofia; Piétri-Rouxel, France; Wood, Matthew J; Voit, Thomas; Lorain, Stéphanie.
Afiliación
  • Peccate C; Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Institut de Myologie, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 105 bd de l'Hôpital, Paris 13, France.
  • Mollard A; Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Institut de Myologie, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 105 bd de l'Hôpital, Paris 13, France.
  • Le Hir M; Université de Versailles St-Quentin, INSERM U1179, LIA BAHN CSM, Montigny-le-Bretonneux, France.
  • Julien L; Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Institut de Myologie, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 105 bd de l'Hôpital, Paris 13, France.
  • McClorey G; Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, OX1 3QX, UK.
  • Jarmin S; School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.
  • Le Heron A; School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.
  • Dickson G; School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.
  • Benkhelifa-Ziyyat S; Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Institut de Myologie, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 105 bd de l'Hôpital, Paris 13, France.
  • Piétri-Rouxel F; Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Institut de Myologie, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 105 bd de l'Hôpital, Paris 13, France.
  • Wood MJ; Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, OX1 3QX, UK.
  • Voit T; Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Institut de Myologie, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 105 bd de l'Hôpital, Paris 13, France.
  • Lorain S; NIHR Biomedical Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Hum Mol Genet ; 25(16): 3555-3563, 2016 08 15.
Article en En | MEDLINE | ID: mdl-27378686
In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Distrofina / Oligonucleótidos Antisentido / Distrofia Muscular de Duchenne / Morfolinos / Distrofia Muscular Animal Límite: Animals / Humans Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2016 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Distrofina / Oligonucleótidos Antisentido / Distrofia Muscular de Duchenne / Morfolinos / Distrofia Muscular Animal Límite: Animals / Humans Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2016 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido