title: Nanoparticles for the delivery of genes and drugs to human hepatocytes.
abstract: Hepatitis B virus envelope L particles form hollow nanoparticles displaying a peptide that is indispensable for liver-specific infection by hepatitis B virus in humans. Here we demonstrate the use of L particles for the efficient and specific transfer of a gene or drug into human hepatocytes both in culture and in a mouse xenograft model. In this model, intravenous injection of L particles carrying the gene for green fluorescent protein (GFP) or a fluorescent dye resulted in observable fluorescence only in human hepatocellular carcinomas but not in other human carcinomas or in mouse tissues. When the gene encoding human clotting factor IX was transferred into the xenograft model using L particles, factor IX was produced at levels relevant to the treatment of hemophilia B. The yeast-derived L particle is free of viral genomes, highly specific to human liver cells and able to accommodate drugs as well as genes. These advantages should facilitate targeted delivery of genes and drugs to the human liver.
authors.affiliation: Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Yamada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tada
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Iwabuki
authors.forename: Marinee K L
authors.initials: MK
authors.lastname: Chuah
authors.forename: Thierry
authors.initials: T
authors.lastname: VandenDriessche
authors.forename: Hideki
authors.initials: H
authors.lastname: Fukuda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ueda
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Tanizawa
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation / Q000379:methods; D005240:Feasibility Studies; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008863:Microspheres; D008969:Molecular Sequence Data; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism*; D010316:Particle Size; D014162:Transfection / Q000379:methods*; D014759:Viral Envelope Proteins / Q000493:pharmacokinetics*
chemical_list: C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins; D004247:DNA