Local Gene Delivery and Methods to Control Immune Responses in Muscles of Normal and Dystrophic Dogs

  • Zejing Wang
  • Stephen J. Tapscott
  • Rainer Storb
Part of the Methods in Molecular Biology book series (MIMB, volume 709)


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.

Key words

Adeno-associated virus AAV Duchenne muscular dystrophy DMD Cellular immunity Muscle Dog cxmd Immunosuppression CSP MMF ATG 



We thank Dr. Jeffery Chamberlain for providing vectors used in the protocols and Dr. Kathy High for providing the c-FIX plasmid. We thank E. Zellmer, Diana Jensen, Jenee O’Brian, and E. Finn for technical assistance, and A. Joslyn, B. Steinmetz, and their teams, and M. Spector, DVM, and J Duncan, DVM, for their care of the dogs. We further thank S. Carbonneau, H. Crawford, B. Larson, K. Carbonneau, Vermeulen, and D. Gayle for administrative assistance and manuscript preparation. This work was supported by NIH U54-HD47175 and the Seattle Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, NIH CA15704, NIH AR056949, and by Career Development Award for Z. Wang from the Muscular Dystrophy Association (MDA 114979).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Zejing Wang
    • 1
  • Stephen J. Tapscott
    • 2
    • 3
  • Rainer Storb
    • 1
  1. 1.Program in Transplantation Biology, Division of Clinical ResearchFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Division of Human BiologyFred Hutchinson Cancer Research CenterSeattleUSA
  3. 3.Department of NeurologyUniversity of WashingtonSeattleUSA

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