Delivery of Condensed DNA by Liposomal Non-viral Gene Delivery System into Nucleus of Dendritic Cells

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  • Nakamura Takashi
    Graduate School of Pharmaceutical Sciences, Hokkaido University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
  • Moriguchi Rumiko
    Graduate School of Pharmaceutical Sciences, Hokkaido University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
  • Kogure Kentaro
    Graduate School of Pharmaceutical Sciences, Hokkaido University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
  • Minoura Arisa
    Graduate School of Pharmaceutical Sciences, Hokkaido University
  • Masuda Tomoya
    Graduate School of Pharmaceutical Sciences, Hokkaido University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
  • Akita Hidetaka
    Graduate School of Pharmaceutical Sciences, Hokkaido University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
  • Kato Kazunori
    Department of Molecular Medicine, Sapporo Medical University
  • Hamada Hirofumi
    Department of Molecular Medicine, Sapporo Medical University
  • Ueno Masaharu
    Faculty of Pharmaceutical Sciences, University of Toyama
  • Futaki Shiroh
    Institute for Chemical Research, Kyoto University Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST)
  • Harashima Hideyoshi
    Graduate School of Pharmaceutical Sciences, Hokkaido University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)

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説明

In this study, we developed novel double-membranous non-viral gene delivery system modified with SV-40 T antigen-derived nuclear localization signal (NLS-DMEND) for delivery of luciferase plasmid DNA to nucleus of non-dividing mouse bone marrow-derived dendritic cells (BMDC). Intracellular trafficking and gene expression of NLS-DMEND in the BMDC were evaluated. Condensed DNA was observed in the nucleus by confocal laser scanning microscopy, and the NLS-DMEND induced significant luciferase activity in the BMDC. It was suggested that the condensed DNA particle transferred into nucleus via energy dependent manner, since the nuclear transfer was inhibited by metabolic inhibitors. In conclusion, condensed plasmid DNA was delivered into the nucleus of non-dividing BMDC by NLS-DMEND.

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