Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine

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  • Kurosaki Tomoaki
    Department of Hospital Pharmacy, Nagasaki University Hospital Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Kodama Yukinobu
    Department of Hospital Pharmacy, Nagasaki University Hospital
  • Muro Takahiro
    Department of Hospital Pharmacy, Nagasaki University Hospital
  • Higuchi Norihide
    Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Nakamura Tadahiro
    Department of Hospital Pharmacy, Nagasaki University Hospital
  • Kitahara Takashi
    Department of Hospital Pharmacy, Nagasaki University Hospital
  • Miyakoda Mana
    Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University
  • Yui Katsuyuki
    Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University
  • Sasaki Hitoshi
    Department of Hospital Pharmacy, Nagasaki University Hospital

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  • Highlighted Paper selected by Editor-in-Chief : Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine

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Abstract

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.

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