Preventive and therapeutic effects of gene therapy using silica nanoparticles-binding of GM-CSF gene on white blood cell production in dogs with leukopenia

Exp Hematol. 2008 Sep;36(9):1091-7. doi: 10.1016/j.exphem.2008.04.002. Epub 2008 Jun 11.

Abstract

Objective: Our previous study has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) gene/silica nanoparticles have a leukocytosis effect in normal dogs. Therefore, this study was conducted to determine whether treatment of canine GM-CSF gene/silica nanoparticles has preventive or therapeutic effects in dogs with leukopenia.

Materials and methods: To induce leukopenia, vinblastine was administered intravenously at a dose of 2 mg/m(2) of body surface area on day 0. Then 7.5 microg GM-CSF/nanoparticles (1:100, w/w) were administered intravenously to each of four dogs in the prevention group on day 2 and an equivalent amount of GM-CSF/nanoparticles was administered to the post-nadir group on day 4 (other groups were administered phosphate-buffered saline intravenously).

Results: Therapeutic GM-CSF gene was expressed in peripheral blood mononuclear cells for 10 days and both the prevention and post-nadir groups showed significant increases in white blood cell counts when compared with the control group, as confirmed by complete blood count, differential count, and flow cytometry.

Conclusions: GM-CSF/nanoparticles can be useful for correction of acute leukopenia, such as chemotherapy-induced myelosuppression, without developing neutralizing antibodies.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cell Count
  • Cytomegalovirus / genetics
  • DNA, Recombinant / administration & dosage
  • DNA, Recombinant / therapeutic use
  • Dogs
  • Drug Carriers
  • Genes, Synthetic
  • Genetic Therapy / methods*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Isoantibodies / biosynthesis
  • Leukocytes / pathology*
  • Leukopenia / blood
  • Leukopenia / chemically induced
  • Leukopenia / therapy*
  • Leukopoiesis*
  • Nanoparticles
  • Promoter Regions, Genetic
  • Silicon Dioxide
  • Simian virus 40 / genetics
  • Transcription, Genetic
  • Vinblastine / toxicity

Substances

  • DNA, Recombinant
  • Drug Carriers
  • Isoantibodies
  • Vinblastine
  • Silicon Dioxide
  • Granulocyte-Macrophage Colony-Stimulating Factor