Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor

Assem Galal Ziady, Jose C. Perales, Thomas Ferkol, Thomas Gerken, Helga Beegen, David H. Perlmutter, Pamela B. Davis

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34 Scopus citations


The serpin enzyme complex receptor (SECR) expressed on hepatocytes binds to a conserved sequence in α1-antitrypsin (α1-AT) and other serpins. A molecular conjugate consisting of a synthetic peptide (C1315) based on the SECR binding motif of human α1-AT covalently coupled to poly-L-lysine was used to introduce reporter genes into hepatoma cell lines in culture. This conjugate condensed DNA into spheroidal particles 18-25 nm in diameter. When transfected with the SECR-directed complex containing pGL3, Hep G2 cells that express the receptor, but not Hep G2 cells that do not, expressed a peak luciferase activity of 538,731 ± 144,346 integrated light units/mg protein 4 days after transfection. Free peptide inhibited uptake and expression in a dose-dependent manner. Complexes of DNA condensed with polylysine or LC- sulfo-N-succinimidyl-3-(2-pyridyldithio)propionate-substituted polylysine were ineffective. Transfection with a plasmid encoding human factor IX produced expression in Hep G2 (high) and HuH7 cells that express SECR but not Hep G2 (low) cells that lack the receptor. Fluorescein-labeled C1315 peptide labeled 9-31% of Hep G2 (high), 10-14% of HUH7, and 0.6-3.4% of Hep G2 (low) cells, and when the lac Z gene was transfected, only these cells expressed β-galactesidase. SECR-mediated gene transfer gives efficient, specific uptake and high-level expression of three reporter genes, and the system merits further study for gene therapy.

Original languageEnglish
Pages (from-to)G545-G552
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number2 36-2
StatePublished - 1997


  • Gene therapy
  • Liver cells
  • Receptor-mediated gene transfer
  • Synthetic peptides


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