In vivo gene delivery by cationic tetraamino fullerene

Rui Maeda-Mamiya, Eisei Noiri, Hiroyuki Isobe, Waka Nakanishi, Koji Okamoto, Kent Doi, Takeshi Sugaya, Tetsuro Izumi, Tatsuya Homma, Eiichi Nakamura

    Research output: Contribution to journalArticle

    133 Citations (Scopus)

    Abstract

    Application of nanotechnology to medical biology has brought remarkable success. Water-soluble fullerenes are molecules with great potential for biological use because they can endow unique characteristics of amphipathic property and form a self-assembled structure by chemical modification. Effective gene delivery in vitro with tetra(piperazino)fullerene epoxide (TPFE) and its superiority to Lipofectin have been described in a previous report. For this study, we evaluated the efficacy of in vivo gene delivery by TPFE. Delivery of enhanced green fluorescent protein gene (EGFP) by TPFE on pregnant female ICR mice showed distinct organ selectivity compared with Lipofectin; moreover, higher gene expression by TPFE was found in liver and spleen, but not in the lung. No acute toxicity of TPFE was found for the liver and kidney, although Lipofectin significantly increased liver enzymes and blood urea nitrogen. In fetal tissues, neither TPFE nor Lipofectin induced EGFP gene expression. Delivery of insulin 2 gene to female C57/BL6 mice increased plasma insulin levels and reduced blood glucose concentrations, indicating the potential of TPFE-based gene delivery for clinical application. In conclusion, this study demonstrated effective gene delivery in vivo for the first time using a water-soluble fullerene.

    Original languageEnglish
    Pages (from-to)5339-5344
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume107
    Issue number12
    DOIs
    Publication statusPublished - 2010 Mar 23

    Keywords

    • Carbon nanotube
    • Gene therapy
    • Green fluorescent protein
    • Insulin 2 gene
    • Toxicity

    ASJC Scopus subject areas

    • General

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  • Cite this

    Maeda-Mamiya, R., Noiri, E., Isobe, H., Nakanishi, W., Okamoto, K., Doi, K., Sugaya, T., Izumi, T., Homma, T., & Nakamura, E. (2010). In vivo gene delivery by cationic tetraamino fullerene. Proceedings of the National Academy of Sciences of the United States of America, 107(12), 5339-5344. https://doi.org/10.1073/pnas.0909223107