Nonviral gene delivery by tetraamino fullerene

Hiroyuki Isobe, Waka Nakanishi, Naoki Tomita, Shigeki Jinno, Hiroto Okayama, Eiichi Nakamura

    Research output: Contribution to journalArticlepeer-review

    89 Citations (Scopus)

    Abstract

    A fullerene derivative bearing two diamino side chains binds to a plasmid vector DNA, either 4 or 40 kbp in size, delivers it to mammalian cells on incubation, and leads to expression of the encoded gene either transiently or stably. The initial physicochemical investigations upon DNA-binding and protective properties of various fullerene compounds against nuclease led us to identify the tetraamino fullerene as an ideal candidate to probe the new concept of fullerene-mediated gene delivery to mammalian cells. Studies on transient and stable transfection of COS-1 cells using green fluorescent protein and luciferase reporter genes revealed several useful properties of the fullerene transfection as compared with the conventional lipid-based transfection method, including much higher efficiency of stable transfection and ability to transfert confluent cells. Chemical and biological studies suggested that the cell uptake of the fullerene/DNA complex takes place by an endocytosis mechanism and that the DNA internalized by endosomes is protected by the fullerene against enzymatic digestion. The stiffness of the fullerene/DNA complex may play some role in the success of the fullerene method.

    Original languageEnglish
    Pages (from-to)124-134
    Number of pages11
    JournalMolecular Pharmaceutics
    Volume3
    Issue number2
    DOIs
    Publication statusPublished - 2006 Mar 1

    Keywords

    • DNA protection
    • Endocytosis
    • Fullerene
    • Stable transfection

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmaceutical Science
    • Drug Discovery

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