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

使用二氧化硅纳米粒子作为载体进行 GM-CSF 基因转移对狗白细胞生成的影响

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作者: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

Conclusions

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

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.

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

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.

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