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Methods Mol Biol. 2011;709:265-75. doi: 10.1007/978-1-61737-982-6_17.

Local gene delivery and methods to control immune responses in muscles of normal and dystrophic dogs.

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  • 1Program in Transplantation Biology, Division of Clinical Research, Fred Hutchinson Cancer Research Center, Fairview Av N, D1-100, Seattle, WA, USA.

Abstract

Adeno-associated viral vector (AAV)-mediated gene transfer represents a promising gene replacement strategy for treating Duchenne muscular dystrophy (DMD). However, recent studies demonstrated cellular immunity specific to AAV capsid proteins in animal models, which resulted in liver toxicity and elimination of transgene expression in a human trial of hemophilia B. We have recently developed immunosuppressive strategies to prevent such immunity for successful long-term transgene expression in dog muscle. Here, we describe in detail the immunosuppressive regimens employed in both normal and DMD dogs and provide methods for evaluating the efficiency of the regimens following intramuscular injection of AAV in dogs.

PMID:
21194034
[PubMed - indexed for MEDLINE]

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