title: In vivo gene delivery by cationic tetraamino fullerene.
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.
authors.affiliation: Department of Chemistry and Exploratory Research for Advanced Technology (Japan Science and Technology Agency), University of Tokyo, 7-3-1 Hongo Bunkyo, Tokyo 113-0033, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Maeda-Mamiya
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Isobe
authors.forename: Waka
authors.initials: W
authors.lastname: Nakanishi
authors.forename: Koji
authors.initials: K
authors.lastname: Okamoto
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Izumi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Homma
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D037741:Fullerenes / Q000737:chemistry / Q000633:toxicity; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D007328:Insulin / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D036103:Nanotechnology; D010714:Phosphatidylethanolamines / Q000633:toxicity; D011247:Pregnancy; D011994:Recombinant Proteins / Q000235:genetics; D012995:Solubility; D014018:Tissue Distribution; D014867:Water
chemical_list: D017931:DNA Primers; D004274:DNA, Recombinant; D037741:Fullerenes; D007328:Insulin; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; C510698:tetraamino fullerene; D014867:Water; D049452:Green Fluorescent Proteins; C020888:1,2-dielaidoylphosphatidylethanolamine