Gene transfer into hepatoma cells mediated by galactose-modified α-helical peptides

Takuro Niidome, Mamiko Urakawa, Haruya Sato, Yoshiyuki Takahara, Toyoaki Anai, Tomomitsu Hatakayama, Akihiro Wada, Toshiya Hirayama, Haruhiko Aoyagi

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

To develop a receptor-mediated gene delivery system into hepatoma cells using the cationic α-helical peptide as the gene carrier molecule, we modified an α-helical peptide, which is known to have transfection abilities into cells, with a multi-antennary ligand containing several galactose residues that provide efficient binding to the asialoglycoprotein receptor. The galactose-modified peptides formed complexes with a plasmid DNA and showed gene transfer abilities into HuH-7 cells, a human hepatoma cell line. The transfection efficiency of the peptide was increased by increasing the number of modified galactose residues on the peptide. Furthermore, considerable inhibition of the transfection efficiency by the addition of asialofetuin, which is a ligand for the asialoglycoprotein receptor, was observed in all galactose-modified peptides. Based on this result, we could confirm that the internalization of the galactose-modified peptides occurred by the receptor-mediated endocytosis pathway. In addition, to understand the transport route of the peptide-DNA complex in the cell, the effects on the transfection efficiencies with several endocytosis inhibitors were examined. As a result, it was suggested that the translocation of the peptide-DNA complex from the endocytic compartments to the cytosol mainly occurred during an early endosome step. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1811-1819
Number of pages9
JournalBiomaterials
Volume21
Issue number17
DOIs
Publication statusPublished - Sep 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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