Lack of Immunotoxicity After Regional Intravenous (RI) Delivery of rAAV to Nonhuman Primate Skeletal Muscle
In: ISSN: 1525-0016, 2010
academicJournal
Zugriff:
International audience ; In the absence of an immune response from the host, intramuscular (IM) injection of recombinant adeno-associated virus (rAAV) results in the permanent expression of the transgene from mouse to primate models. However, recent gene transfer studies into animal models and humans indicate that the risk of transgene and/or capsid-specific immune responses occurs and depends on multiple factors. Among these factors, the route of delivery is important, although poorly addressed in large animal models. Here, we compare the IM and the drug-free regional intravenous (RI) deliveries of rAAV in nonhuman primate (NHP) skeletal muscle monitoring the host immune response toward the transgene. We show that IM is consistently associated with immunotoxicity and the destruction of the genetically modified myofibers, whereas RI allows the stable expression of the transgene. This has important implications for the design of clinical trials for gene transfer in skeletal muscle.
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Lack of Immunotoxicity After Regional Intravenous (RI) Delivery of rAAV to Nonhuman Primate Skeletal Muscle
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Autor/in / Beteiligte Person: | Toromanoff, Alice ; Adjali, Oumeya ; Larcher, Thibaut ; Hill, Marcelo ; Guigand, Lydie ; Chenuaud, Pierre ; Deschamps, Jack-Yves ; Gauthier, Olivier ; Blancho, Gilles ; Vanhove, Bernard ; Rolling, Fabienne ; Cherel, Yan ; Moullier, Philippe ; Anegon, Ignacio ; Le Guiner, Caroline ; UMR649 ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; Centre hospitalier universitaire de Nantes (CHU Nantes) ; Faculté de Médecine ; Université Francois Rabelais Tours ; Développement et Pathologie du Tissu Musculaire (DPTM) ; Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes ; UMR643 ; Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS) ; Department of Molecular Genetics and Microbiology Gainesville (UF|MGM) ; Department of Medicine Gainesville (UF|Medicine) ; University of Florida Gainesville (UF)-University of Florida Gainesville (UF) |
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Zeitschrift: | ISSN: 1525-0016, 2010 |
Veröffentlichung: | HAL CCSD ; Cell Press, 2010 |
Medientyp: | academicJournal |
DOI: | 10.1038/mt.2009.251 |
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