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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3458-3464. Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-07-2908. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2908v1 105/9/3458    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Arruda, V. R. Articles by High, K. A. Search for Related Content PubMed PubMed Citation Articles by Arruda, V. R. Articles by High, K. A. Related Collections Hematopoiesis and Stem Cells Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Regional intravascular delivery of AAV-2-F.IX to skeletal muscle achieves long-term correction of hemophilia B in a large animal model Valder R. Arruda, Hansell H. Stedman, Timothy C. Nichols, Mark E. Haskins, Matthew Nicholson, Roland W. Herzog, Linda B. Couto, and Katherine A. High From the Hematology Division, Department of Pediatrics, and the Howard Hughes Medical Institute, Children's Hospital of Philadelphia, PA; the Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA; the Francis Owen Blood Research Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill; the School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA; andAvigen, Inc,Alameda, CA. In earlier work, we showed that adeno-associated virus–mediated delivery of a Factor IX gene to skeletal muscle by direct intramuscular injection resulted in therapeutic levels of circulating Factor IX in mice. However, achievement of target doses in humans proved impractical because of the large number of injections required. We used a novel intravascular delivery technique to achieve successful transduction of extensive areas of skeletal muscle in a large animal with hemophilia. We provide here the first report of long-term (> 3 years, with observation ongoing), robust Factor IX expression (circulating levels of 4%-14%) by muscle-directed gene transfer in a large animal, resulting in essentially complete correction of the bleeding disorder in hemophilic dogs. The results of this translational study establish an experimental basis for clinical studies of this delivery method in humans with hemophilia B. These findings also have immediate relevance for gene transfer in patients with muscular dystrophy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hemophilia and gene transfer: this dog might hunt Philip R. Johnson Blood 2005 105: 3391. [Full Text] [PDF]

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