Effects of GM-CSF gene transfer using silica-nanoparticles as a vehicle on white blood cell production in dogs.
OBJECTIVE
We sought to test two concepts: that nanoparticles can be used for in vivo gene delivery and that canine granulocyte-macrophage colony-stimulating factor (GM-CSF)/nanoparticles can have possibility to be used to treat transient (acute) canine leukopenia.


METHODS
We have generated a novel fluorescent-silica nanoparticle binding of canine GM-CSF gene; canine GM-CSF gene was inserted between the cytomegalovirus promoter and poly-adenylation sequences of simian virus 40, and the gene construct was ligated to fluorescent silica nanoparticles functionalized with tertiary amine.


RESULTS
When the GM-CSF/nanoparticles were injected into normal dogs, the GM-CSF was expressed in peripheral blood mononuclear cells for at least 9 days and there were significant increases in white blood cell counts, as confirmed by complete blood count, differential count, and flow cytometry. Significant increases in expression of major histocompatibility complex class II on granulocytes and in serum GM-CSF were also observed. Readministration of the nanoparticles was also effective and expression in various tissues was confirmed by reverse transcriptase polymerase chain reaction.


CONCLUSIONS
These GM-CSF/nanoparticles may be useful for correction of acute leukopenia, such as chemotherapy-induced myelosuppression without developing neutralizing antibodies.
Choi
Eun Wha
EW
KRF Zoonotic Disease Priority Research Institute, Department of Veterinary Internal Medicine, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, Korea.
Shin
Il Seob
IS
Chae
Young Jin
YJ
Koo
Hye Cheong
HC
Lee
Jong Hwa
JH
Chung
Tae Ho
TH
Park
Yong Ho
YH
Kim
Dae Yong
DY
Hwang
Cheol Yong
CY
Lee
Chang Woo
CW
Youn
Hwa Young
HY
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006098:Granulocytes / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D007970:Leukopenia / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D053758:Nanoparticles; D012822:Silicon Dioxide / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D012822:Silicon Dioxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor