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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2002-12-3722. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3722v1 102/6/2046    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 Yanay, O. Articles by Osborne, W. R. A. Search for Related Content PubMed PubMed Citation Articles by Yanay, O. Articles by Osborne, W. R. A. Related Collections Hematopoiesis and Stem Cells Phagocytes Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2046-2052 GENE THERAPY Treatment of canine cyclic neutropenia by lentivirus-mediated G-CSF delivery Ofer Yanay, Simon C. Barry, Louis J. Katen, Margaret Brzezinski, Lisa Y. Flint, Jeffrey Christensen, Denny Liggitt, David C. Dale, and William R. A. Osborne From the Departments of Pediatrics, Medicine, and Comparative Medicine, University of Washington, Seattle, WA. Cyclic neutropenia is a rare disease that occurs both in humans and gray collie dogs and is characterized by recurrent severe neutropenia leading to bacterial infections and shortened life expectancy. Daily injections of recombinant granulocyte colony-stimulating factor (rG-CSF) are effective in shortening the period of severe neutropenia and reducing infections. After demonstrating that rG-CSF induced elevated neutrophil production in an affected dog, cytokine administration was stopped and 109 infectious units (IUs) of a lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding canine G-CSF cDNA was administered intramuscularly. Serial blood cell counts showed elevated neutrophil production for longer than 17 months. Although neutrophil counts continued to cycle, the range at nadirs was from 3710 to 5300 cells/µL, well above the nadirs before lentivirus administration. After the injection of lentivirus, mean neutrophil counts ± SD were 12 460 ± 4240 cells/µL, significantly increased over both pretreatment values of 3040 ± 2540 cells/µL (P < .0001) and neutrophil counts during G-CSF administration of 10 290 ± 4860 cells/µL(P < .007). The changes in blood counts from lentivirus injection were associated with absence of clinical signs of infection and fever. The gray collie continued to gain weight and was no longer housed in a pathogen-free environment. Genomic DNA from muscle at injection sites was positive for provirus, whereas gonad, lung, spleen, heart, liver, kidney, leukocytes, and noninjected muscle samples were all negative for provirus. Thus, intramuscular administration of lentivirus encoding G-CSF provided sustained therapeutic levels of neutrophils, suggesting this approach may be applied for long-term treatment of patients with cyclic and other neutropenias. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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