Protocol

Muscle Gene Therapy

Volume 709 of the series Methods in Molecular Biology pp 265-275

Date:

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

  • Zejing WangAffiliated withProgram in Transplantation Biology, Division of Clinical Research, Fred Hutchinson Cancer Research Center
  • , Stephen J. TapscottAffiliated withDivision of Human Biology, Fred Hutchinson Cancer Research CenterDepartment of Neurology, University of Washington
  • , Rainer StorbAffiliated withProgram in Transplantation Biology, Division of Clinical Research, Fred Hutchinson Cancer Research Center

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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.

Key words

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