Partial rescue of growth failure in growth hormone (GH)-deficient mice by a single injection of a double-stranded adeno-associated viral vector expressing the GH gene driven by a muscle-specific regulatory cassette

Hum Gene Ther. 2009 Jul;20(7):759-66. doi: 10.1089/hum.2008.197.


Growth hormone (GH) deficiency (GHD) causes somatic growth impairment. GH has a short half-life and therefore it must be administered by daily subcutaneous injections. Adeno-associated viral (AAV) vectors have been used to deliver genes to animals, and double-stranded AAV (dsAAV) vectors provide widespread and stable transgene expression. In the present study we tested whether an intramuscular injection of dsAAV vector expressing GH under the control of a muscle creatine kinase regulatory cassette would ensure sufficient systemic GH delivery in conjunction with muscle-specific expression. Virus-injected GHD mice showed a significant (p < 0.05) increase in body length and body weight, without reaching full normalization, and significant (p < 0.05) reduction in absolute and relative visceral fat. Quantitative RT-PCR showed preferential GH expression in skeletal muscles that was confirmed by qualitative fluorescence analysis in mice injected with a similar virus expressing green fluorescent protein. The present study shows that systemic GH delivery to GHD animals is possible via a single intramuscular injection of dsAAV carrying a muscle-specific GH-expressing regulatory cassette.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition
  • Body Weight
  • Dependovirus / genetics*
  • Femur / pathology
  • Gene Expression Regulation
  • Genetic Therapy
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Growth Disorders / genetics
  • Growth Disorders / pathology
  • Growth Disorders / therapy*
  • Growth Hormone / blood
  • Growth Hormone / deficiency
  • Growth Hormone / genetics*
  • Growth Hormone / therapeutic use*
  • Injections, Subcutaneous
  • Insulin-Like Growth Factor I / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Muscles / pathology*
  • Organ Specificity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Tibia / pathology


  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Growth Hormone