Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine
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概要
- 論文の詳細を見る
In this experiment, we developed a novel safe and effective gene delivery vector coated with γ-polyglutamic acid (γ-PGA-coated complexes). The γ-PGA-coated complex was composed of chiseled spherical nano-particles with anionic charges. The plasmid DNA/polyethyleneimine complex (non-coated complex) showed high transgene efficiency in the spleen and lung after intravenous administration in mice, with high liver toxicity and lethality. On the other hand, γ-PGA-coated complex selectively showed high transgene efficiency in the spleen without such toxicity. Furthermore, the γ-PGA-coated complex highly accumulated and showed high gene expression in the marginal zone of the spleen. Those results strongly indicated that γ-PGA-coated complex was suitable as a DNA vaccine vector. We therefore applied γ-PGA-coated complex to melanoma DNA vaccine, pUb-M. The γ-PGA-coated complex containing pUb-M significantly inhibited the growth and metastasis of a melanoma cell line, B16-F10 cells. In conclusion, we developed a splenic gene vector, γ-PGA-coated complex, as a novel technology for clinical vaccination.
- 公益社団法人 日本薬学会の論文
著者
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KODAMA Yukinobu
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Yui Katsuyuki
Division Of Immunology Department Of Molecular Microbiology And Immunology Graduate School Of Biomed
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Muro Takahiro
Department Of Pharmacy Iizuka Hospital:pharmaceutical Sciences Fukuoka University Graduate School
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Kitahara Takashi
Department Of Breast Oncology Cancer Institute Hospital Of Japanese Foundation For Cancer Research
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Nakamura Tadahiro
Department of Hospital Pharmacy, Nagasaki University Hospital
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Kurosaki Tomoaki
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Higuchi Norihide
Department of Hospital Pharmacy, Nagasaki University Hospital
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Miyakoda Mana
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University
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Higuchi Norihide
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Muro Takahiro
Department of Hospital Pharmacy, Nagasaki University Hospital
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