Use of a Lower Dosage Liver-Detargeted AAV Vector to Prevent Hamster Muscular Dystrophy
| Autor: | Giulio Piluso, Michele Iacomino, Ida Luisa Rotundo, Alberto Auricchio, Gerardo Nigro, Alessio Lancioni, Vincenzo Nigro, Marco Savarese, Luca D'Orsi |
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| Přispěvatelé: | Rotundo, Il, Lancioni, A, Savarese, M, D'Orsi, L, Iacomino, M, Nigro, G, Piluso, G, Auricchio, Alberto, Nigro, V., Nigro, Gerardo, Piluso, Giulio, Auricchio, A, Nigro, Vincenzo |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
musculoskeletal diseases DNA Complementary viruses Transgene Genetic Vectors Hamster Biology Muscular Dystrophies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cricetinae Sarcoglycans Complementary DNA Genetics medicine Animals Transgenes Muscular dystrophy Muscle Skeletal Receptor Molecular Biology Research Articles 030304 developmental biology 0303 health sciences Skeletal muscle Genetic Therapy Heparan sulfate Dependovirus medicine.disease Molecular biology 3. Good health medicine.anatomical_structure Liver chemistry Molecular Medicine Ectopic expression 030217 neurology & neurosurgery |
| Zdroj: | Human Gene Therapy; Vol 24 |
| ISSN: | 1557-7422 |
| DOI: | 10.1089/hum.2012.121 |
| Popis: | "Abstract The BIO14.6 hamster carries a mutation in the delta sarcoglycan gene causing muscular dystrophy and cardiomyopathy. The disease can be prevented by systemic delivery of delta sarcoglycan cDNA using adeno-associated viruses (AAVs). However, all AAVs also target the liver, raising concerns about their therapeutic efficacy in human applications. We compared the AAV2/8 with the chimeric AAV2/2i8, in which the 585-QQNTAP-590 motif of the AAV8 serotype was added to the heparan sulfate receptor footprint of the AAV2 strain. Both vectors carrying the human delta sarcoglycan cDNA were delivered into 24 14-day-old BIO14.6 hamsters. We followed transgene expression in muscle and liver for 7 months. We detected a sustained ectopic expression of delta sarcoglycan in the liver when using AAV2/8 but not AAV2/2i8. Genomic copies of AAV2/2i8 were not detectable in the liver, while at least 100-fold more copies of AAV2/8 were counted. In contrast, the hamster skeletal muscle expressed more delta sarcoglycan using AAV2/2i8 and were still healthy after 7 months at the lower dosage. We conclude that this chimeric vector is a robust option for safer and longer-term diseased muscle targeting." |
| Databáze: | OpenAIRE |
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