Efficient delivery of immunostimulatory DNA to mouse and human immune cells through the construction of polypod-like structured DNA

Nanomedicine : Nanotechnology, Biology, and Medicine
Shota UnoYoshinobu Takakura

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. This study demonstrates the utility of polypoid-like structured DNA (polypodna) preparations as potent immunostimulators in a murine model.

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Citations

Apr 4, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kohta MohriYoshinobu Takakura
Sep 15, 2015·Nanomedicine : Nanotechnology, Biology, and Medicine·Yu NishidaMakiya Nishikawa
Apr 28, 2016·Chemical Society Reviews·Di Sheng LeeDavid Tai Leong
Jul 30, 2015·Biomaterials Science·Wujin Sun, Zhen Gu
Jul 23, 2019·Nucleic Acid Therapeutics·Fusae KomuraMakiya Nishikawa
Feb 18, 2020·Frontiers in Pharmacology·Qingjia ChiHuaping Liang
Sep 23, 2020·Chembiochem : a European Journal of Chemical Biology·Dhiraj BhatiaLudger Johannes
Jun 15, 2018·International Journal of Pharmaceutics·Daiki NomuraMakiya Nishikawa
Mar 29, 2021·Nanomedicine : Nanotechnology, Biology, and Medicine·Keisuke UmemuraMakiya Nishikawa

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