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 × 109 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/µl, which was significantly increased over both the pretreatment value (5,240 ± 4,800 cells/µl; p < 0.0001) and the neutrophil count during G-CSF administration (17,820 ± 11,100 cells/µl; p < 0.0001). By systemic infusion of recombinant G-CSF to normal dogs we estimated that 2 × 109 IU of lentivirus delivered 3.5 µg of G-CSF per kilogram per day. After lentiviral vector treatment the gray collie gained weight, showed no clinical signs of infection ...