Nanoparticles for the delivery of genes and drugs to human hepatocytes

Tadanori Yamada, Yasushi Iwasaki, Hiroko Tada, Hidehiko Iwabuki, Marinee K.L. Chuah, Thierry VandenDriessche, Hideki Fukuda, Akihiko Kondo, Masakazu Ueda, Masaharu Seno, Katsuyuki Tanizawa, Shun'ichi Kuroda

Research output: Contribution to journalArticle

213 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)885-890
Number of pages6
JournalNature Biotechnology
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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