Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/34056
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Type: Journal article
Title: Treatment of canine cyclic neutropenia by lentivirus-mediated G-CSF delivery
Author: Yanay, O.
Barry, S.
Katen, L.
Brzezinski, M.
Flint, L.
Christensen, J.
Liggitt, D.
Dale, D.
Osborne, W.
Citation: Blood, 2003; 102(6):2046-2052
Publisher: Amer Soc Hematology
Issue Date: 2003
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
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
Abstract: 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/microL, well above the nadirs before lentivirus administration. After the injection of lentivirus, mean neutrophil counts +/- SD were 12 460 +/- 4240 cells/microL, significantly increased over both pretreatment values of 3040 +/- 2540 cells/microL(P <.0001) and neutrophil counts during G-CSF administration of 10 290 +/- 4860 cells/microL(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.
Keywords: Neutrophils
Hela Cells
Animals
Dogs
Humans
Lentivirus
Neutropenia
Disease Models, Animal
Granulocyte Colony-Stimulating Factor
Leukocyte Count
Transgenes
Male
Genetic Therapy
Description: Copyright © 2003 by American Society of Hematology
DOI: 10.1182/blood-2002-12-3722
Description (link): http://bloodjournal.hematologylibrary.org/cgi/content/abstract/102/6/2046
Appears in Collections:Aurora harvest 6
Paediatrics publications

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