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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 (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 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 Social Bookmarking                   What's this? Submitted December 6, 2002 Accepted May 9, 2003 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* Department of Pediatrics, University of Washington, Seattle, WA, USA Department of Medicine, University of Washington, Seattle, WA, USA Department of Comparative Medicine, University of Washington, Seattle, WA, USA * Corresponding author; email: wosborne{at}u.washington.edu. Cyclic neutropenia is a rare disease that occurs both in humans and grey 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 (G-CSF) are effective in shortening the period of severe neutropenia and reducing infections. After demonstrating that recombinant G-CSF induced elevated neutrophil production in an affected dog, cytokine administration was stopped and 109 infectious units (IU) of a lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding canine G-CSF cDNA was administered intramuscularly (IM). Serial blood cell counts showed elevated neutrophil production for over 17 months. Although neutrophil counts continued to cycle, the range at nadirs was from 3,710 to 5,300 cells/µL, well above the nadirs before lentivirus administration. After the injection of lentivirus mean neutrophil counts±SD were 12,460±4,240 cells/µL, significantly increased over both pretreatment values of 3,040±2,540 cells/µL (p<0.0001) and neutrophil counts during G-CSF administration of 10,290±4,860 cells/µL (p<0.007). The changes in blood counts from lentivirus injection were associated with absence of clinical signs of infection and fever. The grey 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 non injected muscle samples were all negative. Thus, IM 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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