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Journal of Virology, February 2000, p. 1436-1442, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Full Functional Rescue of a Complete Muscle (TA) in Dystrophic Hamsters by Adeno-Associated Virus Vector-Directed Gene Therapy

Xiao Xiao,1,2,* Juan Li,1,2 Yeou-Ping Tsao,1,2,3 Devin Dressman,1,2 Eric P. Hoffman,1,2,4 and Jon F. Watchko2,5

Department of Molecular Genetics and Biochemistry,1 Duchenne Muscular Dystrophy Research Center (DMDRC),2 and Department of Pediatrics and Magee-Women's Research Institute,5 University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; National Defense Medical Center, Taipei, Taiwan3; and Research Center for Genetic Medicine, Children's National Medical Center, Washington, D.C.4

Received 17 August 1999/Accepted 9 October 1999

Limb girdle muscular dystrophy (LGMD) 2F is caused by mutations in the delta -sarcoglycan (SG) gene. Previously, we have shown successful application of a recombinant adeno-associated virus (AAV) vector for genetic and biochemical rescue in the Bio14.6 hamster, a homologous animal model for LGMD 2F (J. Li et al., Gene Ther. 6:74-82, 1999). In this report, we show efficient and long-term delta -SG expression accompanied by nearly complete recovery of physiological function deficits after a single-dose AAV vector injection into the tibialis anterior muscle of the dystrophic hamsters. AAV vector treatment led to more than 97% recovery in muscle strength for both the specific twitch force and the specific tetanic force, when compared to the age-matched control. Vector treatment also prevented pathological muscle hypertrophy and resulted in normal muscle weight and size. Finally, vector-treated muscle showed substantial improvement of the histopathology. This is the first report of successful functional rescue of an entire muscle after AAV-mediated gene delivery. This report also demonstrates the feasibility of in vivo gene therapy for LGMD patients by using AAV vectors.

* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, Room W1244, BST, University of Pittsburgh, Pittsburgh, PA 15261. Phone: (412) 648-9487. Fax: (412) 624-1401. E-mail: xiaox+{at}pitt.edu.

Journal of Virology, February 2000, p. 1436-1442, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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