Size reduction of galactosylated PEI/DNA complexes improves lectin-mediated gene transfer into hepatocytes.
Hepatocytes are interesting targets for gene therapy applications. Several hepatocyte-directed gene delivery vectors have been described. For example, simple galactosyl residues coupled to polyethylenimine (PEI) gave an efficient vector which selectively transfected hepatocytes via the asialoglycoprotein receptor-mediated endocytosis [Zanta, M. A., et al. (1997) Bioconjugate Chem. 8, 839-844]. However, the large size of these galactosylated PEI/DNA complexes prevented their use in vivo. We have investigated the role of the saccharide length on the size of glycosylated-PEI/DNA particles. When 5% of the PEI nitrogens were grafted with a linear tetragalactose structure (lGal4), small and stable particles were formed upon complexation with plasmid DNA. These particles were essentially toroids having a size of 50-80 nm and a zeta-potential close to neutrality. Moreover, these slightly charged PEI-lGal4/DNA complexes were as selective as the previously described galactosylated-PEI vector to transfect hepatocytes, but in addition, they were more efficient. It is expected that the properties of the PEI-lGal4/DNA complexes may increase their diffusion into the liver and their efficiency to transfect hepatocytes.
Laboratoire de Chimie Génétique, Faculté de Pharmacie, CNRS (UMR 7514) et Université Louis Pasteur de Strasbourg, BP 24, F-67401 Illkirch Cedex, France.
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Remy
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Erbacher
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D005690:Galactose / Q000737:chemistry*; D018014:Gene Transfer Techniques; D037102:Lectins / Q000737:chemistry*; D008099:Liver / Q000166:cytology*; D051379:Mice; D008970:Molecular Weight; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection
D037102:Lectins; D011094:Polyethyleneimine; D004247:DNA; D005690:Galactose