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- Title
In vivo targeted gene transfer into liver cells mediated by a novel galactosyl-D-lysine/D-serine copolymer.
- Authors
Hisayasu, S; Miyauchi, M; Akiyama, K; Gotoh, T; Satoh, S; Shimada, T
- Abstract
A novel synthetic polypeptide designed as a DNA bindingmolecule for liver-specific, receptor-mediated, gene transfer was used to selectively introduce reporter genes into liver cells in the form of plasmid DNA–ligand complexes. The polypeptide was a D-lysine/D-serine copolymer (Lys/Ser = 33/36 or 53/60) modified with a polyethylene glycol 5000 at the carboxyl-terminus (PLSP). In addition, the lysine ε-amino groups were covalently bound to galactose (galactosyl-PLSP), a ligand for the asialoglycoprotein receptor on hepatocytes. Solutions of DNA–ligand complex were prepared by adding solutions of DNA and galactosyl-PLSP in a mixing ratio of DNA:galactosyl-PLSP = 1:3 (w/w). Following injection of the DNA–ligand complex into mice via the tail vein, high levels of luciferase and enhanced green fluorescent protein, which were encoded by the reporter genes, were observed in liver. In contrast, luciferase activity in kidney, spleen, lung and heart was negligible. The high levels of gene expression obtained with DNA/galactosyl-PLSP complexes were achieved without partial hepatectomy or administration of lysosomotrophic agents. Thus, the synthetic Lys/Ser copolymer used in the present study appears to be a promising new tool which enhances the efficacy of receptor-mediated gene transfer into hepatocytes and which may provide another step toward the clinical practice of organ-specific gene therapy.
- Subjects
PEPTIDES; GENETIC transformation; DNA-binding proteins; LIVER cells; DNA-ligand interactions; THERAPEUTICS
- Publication
Gene Therapy, 1999, Vol 6, Issue 4, p689
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3300868