Effects of GM-CSF gene transfer using silica-nanoparticles as a vehicle on white blood cell production in dogs.

Abstract

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.

MATERIALS AND 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.

• Authors: Eun Wha Choi, Il Seob Shin, Young Jin Chae, Hye Cheong Koo, Jong Hwa Lee, Tae Ho Chung, Yong Ho Park, Dae Yong Kim, Cheol Yong Hwang, Chang Woo Lee, Hwa Young Youn
• Journal: Experimental hematology (Exp Hematol) Vol. 36 Issue 7 Pg. 807-15 (Jul 2008) ISSN: 0301-472X [Print] Netherlands
• PMID: 18375041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histocompatibility Antigens Class II
• Silicon Dioxide
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Acute Disease
• Animals
• Dogs
• Gene Expression (genetics)
• Gene Expression Regulation (genetics)
• Gene Transfer Techniques
• Genetic Therapy
• Granulocyte-Macrophage Colony-Stimulating Factor (biosynthesis, genetics)
• Granulocytes (metabolism)
• Histocompatibility Antigens Class II (biosynthesis, genetics)
• Leukocytes, Mononuclear (metabolism)
• Leukopenia (genetics, metabolism, therapy)
• Nanoparticles
• Silicon Dioxide (pharmacology)