An adult dog with cyclic neutropenia treated by lentivirus- mediated delivery of granulocyte colony-stimulating factor.
Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by recurrent neutropenia, and is treated by daily injections of recombinant granulocyte colony-stimulating factor (G-CSF). After showing that canine recombinant G-CSF increased neutrophil counts in an affected dog, we administered intramuscularly 2 x 10(9) infectious units (IU) of a lentiviral vector encoding canine G-CSF cDNA. Elevated, therapeutic neutrophil production was obtained for nearly 18 months. Lentiviral vector treatment provided a mean neutrophil count of 29,230 +/- 12,930 cells/microl, which was significantly increased over both the pretreatment value (5,240 +/- 4,800 cells/microl; p < 0.0001) and the neutrophil count during G-CSF administration (17,820 +/- 11,100 cells/microl; p < 0.0001). By systemic infusion of recombinant G-CSF to normal dogs we estimated that 2 x 10(9) IU of lentivirus delivered 3.5 microg of G-CSF per kilogram per day. After lentiviral vector treatment the gray collie gained weight, showed no clinical signs of infection and fever, and no longer needed housing in a pathogen-free environment. Genomic DNA harvested from muscle at the injection sites was positive for provirus, whereas gonad, lung, spleen, heart, liver, kidney, and noninjected muscle samples were negative. These studies show that an adult animal is responsive long-term to lentivirus-mediated G-CSF delivery, suggesting this approach may be applied for treatment of adult patients with cyclic and other neutropenias.
Yanay
Ofer
O
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Brzezinski
Margaret
M
Christensen
Jeffrey
J
Liggitt
Denny
D
Dale
David C
DC
Osborne
William R A
WR
D000818:Animals; D004283:Dog Diseases / Q000235:genetics / Q000628:therapy*; D004285:Dogs; D015316:Genetic Therapy; D005822:Genetic Vectors; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000627:therapeutic use; D016086:Lentivirus; D009503:Neutropenia / Q000235:genetics / Q000628:therapy / Q000662:veterinary*; D011994:Recombinant Proteins; D013997:Time Factors
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor