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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2003-01-0292. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0292v1 102/6/2031    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Scallan, C. D. Articles by Couto, L. B. Search for Related Content PubMed PubMed Citation Articles by Scallan, C. D. Articles by Couto, L. B. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2031-2037 GENE THERAPY Sustained phenotypic correction of canine hemophilia A using an adeno-associated viral vector Ciaran D. Scallan, David Lillicrap, Haiyan Jiang, Xiaobing Qian, Susannah L. Patarroyo-White, Amy E. Parker, Tongyao Liu, Joseph Vargas, Dea Nagy, Sharon K. Powell, J. Fraser Wright, Patricia V. Turner, Shawn J. Tinlin, Sandra E. Webster, Alan McClelland, and Linda B. Couto From Avigen, Inc, Alameda, CA; Department of Pathology, Queen's University, Kingston, ON, Canada; and Department of Pathobiology, Ontario Veterinary College, Guelph, ON, Canada. Gene therapy for hemophilia A requires efficient delivery of the factor VIII gene and sustained protein expression at circulating levels of at least 1% to 2% of normal. Adeno-associated viral type 2 (AAV2) vectors have a number of advantages over other viral vectors, including an excellent safety profile and persistent gene expression. However, a major disadvantage is their small packaging capacity, which has hampered their use in treating diseases such as hemophilia A, cystic fibrosis, and muscular dystrophy, which are caused by mutations in large genes. Here we demonstrate that this can be overcome by using small regulatory elements to drive expression of a B-domain–deleted form of FVIII. The use of this vector for hepatic gene transfer in a canine model of hemophilia A resulted in the sustained (> 14 months) expression of biologically active FVIII. FVIII activity levels of 2% to 4% were achieved. These levels correlated with a partial correction in the whole-blood clotting time and cuticle bleeding time. In addition, immunoprecipitation analysis demonstrated the expression of canine FVIII of the predicted size in the plasma of injected animals. These data support the use of AAV2 vectors in human clinical trials to treat hemophilia A patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Mingozzi, N. C. Hasbrouck, E. Basner-Tschakarjan, S. A. Edmonson, D. J. Hui, D. E. Sabatino, S. Zhou, J. F. Wright, H. Jiang, G. F. Pierce, et al. Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver Blood, October 1, 2007; 110(7): 2334 - 2341. [Abstract] [Full Text] [PDF] H. Jiang, D. Lillicrap, S. Patarroyo-White, T. Liu, X. Qian, C. D. Scallan, S. Powell, T. Keller, M. McMurray, A. Labelle, et al. Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs Blood, July 1, 2006; 108(1): 107 - 115. [Abstract] [Full Text] [PDF] C. D. Scallan, H. Jiang, T. Liu, S. Patarroyo-White, J. M. Sommer, S. Zhou, L. B. Couto, and G. F. 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