http://www.nature.co...abs/nbt843.htmlPublished online: 29 June 2003, doi:10.1038/nbt843
August 2003 Volume 21 Number 8 pp 885 - 890
Nanoparticles for the delivery of genes and drugs to human hepatocytesTadanori Yamada1, 2, Yasushi Iwasaki3, Hiroko Tada4, Hidehiko Iwabuki1, 5, Marinee KL Chuah6, Thierry VandenDriessche6, Hideki Fukuda2, Akihiko Kondo7, Masakazu Ueda3, 8, Masaharu Seno4, Katsuyuki Tanizawa1 & Shun'ichi Kuroda1
1. Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
2. Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan.
3. Keio University, School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
4. Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka, Okayama 700-8530, Japan.
5. Japan Science and Technology Corporation (JST), 5-3 Yonbancho, Chiyoda, Tokyo 102-8666, Japan.
6. Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology–University of Leuven, 49 Herestraat, B-3000 Leuven, Belgium.
7. Faculty of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan.
8. Beacle Inc., 2-10-13 Kadota-Bunka, Okayama, Okayama 703-8273, Japan.
Correspondence should be addressed to S Kuroda. e-mail: skuroda@sanken.osaka-u.ac.jp
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.