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.
Bettinger
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Laboratoire de Chimie Génétique, Faculté de Pharmacie, CNRS (UMR 7514) et Université Louis Pasteur de Strasbourg, BP 24, F-67401 Illkirch Cedex, France.
Remy
J S
JS
Erbacher
P
P
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