title: Intranasal gene delivery with a polyethylenimine-PEG conjugate.
abstract: Polyethylenimines (PEIs) are among the most efficient synthetic DNA carriers. High levels of reporter gene expression can be obtained with these agents on a variety of cells. Nevertheless, the gap between their efficiency and that required for therapeutic approaches is still important. With the aim to improve the in vivo transfection properties of PEIs, we have synthesized a conjugate consisting of the linear polymer of 22 kDa covalently modified with polyethyleneglycol (PEG) residues. The resulting conjugate was able to complex DNA and allowed the preparation of highly concentrated polyplexes, in contrast to non-modified PEIs. Administration by nasal instillation of PEI-PEG/DNA complexes in mice resulted in significant levels of transgene expression. Luciferase activity was greatest 24 h after delivery and decreased thereafter. Our results show that the grafting of PEGs can improve some of the properties of PEIs.
authors.affiliation: Généthon III-CNRS URA 1923, 1 Rue de l'Internationale, Evry, France. akich@genethon.fr
authors.forename: Antoine
authors.initials: A
authors.lastname: Kichler
authors.forename: Miguel
authors.initials: M
authors.lastname: Chillon
authors.forename: Christian
authors.initials: C
authors.lastname: Leborgne
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
authors.forename: Benoît
authors.initials: B
authors.lastname: Frisch
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D015870:Gene Expression; D017930:Genes, Reporter; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry*; D014162:Transfection
chemical_list: D004337:Drug Carriers; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA