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


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.
KRF Zoonotic Disease Priority Research Institute, Research Institute of Veterinary Science, Seoul National University, Seoul, Republic of Korea.
Eun Wha
EW
Choi
Hye Cheong
HC
Koo
Il Seob
IS
Shin
Young Jin
YJ
Chae
Jong Hwa
JH
Lee
Sei Myoung
SM
Han
Seung Jun
SJ
Lee
Dong Ha
DH
Bhang
Yong Ho
YH
Park
Chang Woo
CW
Lee
Hwa Young
HY
Youn
D000818:Animals; D001772:Blood Cell Count; D003587:Cytomegalovirus / Q000235:genetics; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000627:therapeutic use; D004285:Dogs; D004337:Drug Carriers; D005813:Genes, Synthetic; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology; D007518:Isoantibodies / Q000096:biosynthesis; D007962:Leukocytes / Q000473:pathology*; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced / Q000628:therapy*; D019891:Leukopoiesis; D053758:Nanoparticles; D011401:Promoter Regions, Genetic; D012822:Silicon Dioxide; D013539:Simian virus 40 / Q000235:genetics; D014158:Transcription, Genetic; D014747:Vinblastine / Q000633:toxicity
D004274:DNA, Recombinant; D004337:Drug Carriers; D007518:Isoantibodies; D014747:Vinblastine; D012822:Silicon Dioxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor