title: Efficient delivery of immunostimulatory DNA to mouse and human immune cells through the construction of polypod-like structured DNA.
abstract: Investigation of mouse macrophage-like RAW264.7 cells showed that the immunostimulatory activity of CpG DNA is increased by formation of polypod-like structured DNA (polypodna), an assembly consisting of three or more oligodeoxynucleotides. To apply CpG polypodna to immunotherapy, its activity was examined in murine dendritic DC2.4 cells, splenic macrophages, and bone marrow-derived dendritic cells (BMDCs). In all cell types, increasing the pod number increased the cellular uptake of DNA and cytokine release. No significant release of cytokines was observed in macrophages lacking Toll-like receptor 9. Similar results were obtained after intradermal injection of polypodna. The polypodna preparations produced significantly higher amounts of interferon α in human peripheral blood mononuclear cells (PBMCs) compared with single-stranded DNA. The conditioned medium of hexapodna-treated human PBMCs effectively inhibited the activity of a hepatitis C virus subgenomic replicon reporter system. These results indicate that polypodna preparations are useful as an immunostimulator.
  
  
  BACKGROUND
  This study demonstrates the utility of polypoid-like structured DNA (polypodna) preparations as potent immunostimulators in a murine model.
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Shota
authors: S
authors: Uno
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto, Japan. Electronic address: makiya@pharm.kyoto-u.ac.jp.
authors: Makiya
authors: M
authors: Nishikawa
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Kohta
authors: K
authors: Mohri
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Yuka
authors: Y
authors: Umeki
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Noriyuki
authors: N
authors: Matsuzaki
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Yuki
authors: Y
authors: Takahashi
authors: Department of Haematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Haruyuki
authors: H
authors: Fujita
authors: Department of Haematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Norimitsu
authors: N
authors: Kadowaki
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Yoshinobu
authors: Y
authors: Takakura
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice
chemical_list: D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D004247:DNA
keywords: CpG DNA; Dendritic cell; Peripheral blood mononuclear cell; Toll-like receptor 9