Gene Therapy in Skeletal Muscle Mediated by Adeno-Associated Virus Vectors

  • Chunping Qiao
  • Taeyoung Koo
  • Juan Li
  • Xiao XiaoEmail author
  • J. George Dickson
Part of the Methods in Molecular Biology book series (MIMB, volume 807)


Adeno-associated virus (AAV) is the most promising gene delivery vehicle for muscle-directed gene therapy. AAV’s natural tropism to muscle cells, long-term persistent transgene expression, multiple serotypes, as well as its minimal immune response have made AAV vectors well suited for muscle-directed gene therapy. AAV vector-mediated gene delivery to augment muscle structural proteins, such as dystrophin and sarcoglycans, offers great hope for muscular dystrophy patients. In addition, muscle can be used as a therapeutic platform for AAV vectors to express nonmuscle secretory/regulatory pathway proteins for diabetes, atherosclerosis, hemophilia, cancer, etc. AAV vector can be delivered into both skeletal muscle and cardiac muscle by means of local, regional, and systemic administrations. Successful animal studies have led to several noteworthy clinical trials involving muscle-directed gene therapy. In this chapter, we describe the basic methodology that is currently utilized in the area of AAV-mediated muscle-directed gene therapy. These methods include vector delivery route, vector dosage, detection of transgene expression by immunostaining and western blot, determination of vector copy numbers and quantification of mRNA expression, as well as potential immune responses involved in AAV delivery. Technical details and tips leading to successful experimentation are also discussed.

Key words

Muscle-directed gene therapy Adeno-associated virus Vector-mediated gene delivery Dystrophin Sarcoglycans Muscular dystrophy Transgene expression Vector dosage 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Chunping Qiao
    • 1
  • Taeyoung Koo
    • 2
  • Juan Li
    • 1
  • Xiao Xiao
    • 1
    Email author
  • J. George Dickson
    • 2
  1. 1.Division of Molecular PharmaceuticsUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.School of Biological SciencesRoyal Holloway – University of LondonLondonUK

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