Improved transduction of canine X-linked muscular dystrophy with rAAV9-microdystrophin via multipotent MSC pretreatment
| العنوان: | Improved transduction of canine X-linked muscular dystrophy with rAAV9-microdystrophin via multipotent MSC pretreatment |
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| المؤلفون: | Tomoko Chiyo, Yuko Nitahara-Kasahara, Hiromi Hayashita-Kinoh, Mutsuki Kuraoka, Shin'ichi Takeda, Takashi Okada, Hironori Okada, Posadas-Herrera Guillermo |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 20, Iss, Pp 133-141 (2021) Molecular Therapy. Methods & Clinical Development |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, medicine.medical_specialty, Stromal cell, lcsh:QH426-470, Duchenne muscular dystrophy, Transgene, viruses, microdystrophin, MSC, 03 medical and health sciences, 0302 clinical medicine, DMD, Genetics, medicine, X-linked muscular dystrophy, lcsh:QH573-671, Molecular Biology, Liver injury, DMD dog model, immune modulation, biology, business.industry, lcsh:Cytology, Mesenchymal stem cell, Neurotoxicity, AAV, medicine.disease, lcsh:Genetics, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, Original Article, Dystrophin, business |
| الوصف: | Duchenne muscular dystrophy (DMD) is a severe congenital disease associated with mutation of the dystrophin gene. Supplementation of dystrophin using recombinant adeno-associated virus (rAAV) has promise as a treatment for DMD, although vector-related general toxicities, such as liver injury, neurotoxicity, and germline transmission, have been suggested in association with the systemic delivery of high doses of rAAV. Here, we treated normal or dystrophic dogs with rAAV9 transduction in conjunction with multipotent mesenchymal stromal cell (MSC) injection to investigate the therapeutic effects of an rAAV expressing microdystrophin (μDys) under conditions of immune modulation. Bone-marrow-derived MSCs, rAAV-CMV-μDys, and a rAAV-CAG-luciferase (Luc) were injected into the jugular vein of a young dystrophic dog to induce systemic expression of μDys. One week after the first injection, the dog received a second intravenous injection of MSCs, and on the following day, rAAV was intravenously injected into the same dog. Systemic injection of rAAV9 with MSCs pretreatment improves gene transfer into normal and dystrophic dogs. Dystrophic phenotypes significantly improved in the rAAV-μDys-injected dystrophic dog, suggesting that an improved rAAV-μDys treatment including immune modulation induces successful long-term transgene expression to improve dystrophic phenotypes. Graphical Abstract We treated normal or dystrophic dogs with rAAV9 transduction with MSCs to investigate the therapeutic effects of an rAAV-μDys under immune modulation. Systemic injection of rAAV9 with MSCs pretreatment improves gene transfer into dogs. An improved rAAV-μDys treatment including immune modulation induces successful long-term transgene expression to improve dystrophic phenotypes. |
| اللغة: | English |
| تدمد: | 2329-0501 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f27cdd7fae5823ace9af4578935a680 http://www.sciencedirect.com/science/article/pii/S2329050120302308 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5f27cdd7fae5823ace9af4578935a680 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23290501 |
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