Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
PLANK, C; ZATLOUKAL, K; COTTEN, M; MECHTLER, K; WAGNER, E.
Gene transfer into hepatocytes using asialoglycoprotein receptor mediated endocytosis of DNA complexed with an artificial tetra-antennary galactose ligand.
Bioconjug Chem. 1992; 3(6):533-539
Doi: 10.1021/bc00018a012
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- Co-Autor*innen der Med Uni Graz
- Zatloukal Kurt
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- Abstract:
- We have constructed an artificial ligand for the hepatocyte-specific asialoglycoprotein receptor for the purpose of generating a synthetic delivery system for DNA. This ligand has a tetra-antennary structure, containing four terminal galactose residues on a branched carrier peptide. The carbohydrate residues of this glycopeptide were introduced by reductive coupling of lactose to the alpha- and epsilon-amino groups of the two N-terminal lysines on the carrier peptide. The C-terminus of the peptide, containing a cysteine separated from the branched N-terminus by a 10 amino acid spacer sequence, was used for conjugation to 3-(2-pyridyldithio)propionate-modified polylysine via disulfide bond formation. Complexes containing plasmid DNA bound to these galactose-polylysine conjugates have been used for asialoglycoprotein receptor-mediated transfer of a luciferase gene into human (HepG2) and murine (BNL CL.2) hepatocyte cell lines. Gene transfer was strongly promoted when amphipathic peptides with pH-controlled membrane-disruption activity, derived from the N-terminal sequence of influenza virus hemagglutinin HA-2, were also present in these DNA complexes. Thus, we have essentially borrowed the small functional domains of two large proteins, asialoglycoprotein and hemagglutinin, and assembled them into a supramolecular complex to generate an efficient gene-transfer system.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Asialoglycoprotein Receptor -
- Asialoglycoproteins - metabolism
- Cells, Cultured - metabolism
- DNA - chemistry
- Endocytosis - chemistry
- Galactose - chemistry
- Humans - chemistry
- Ligands - chemistry
- Liver - cytology
- Luciferases - genetics
- Mice - genetics
- Molecular Sequence Data - genetics
- Plasmids - genetics
- Receptors, Immunologic - metabolism
- Transfection - methods