title: Cyclodextrin-polyethylenimine conjugates for targeted in vitro gene delivery.
abstract: Many human gene therapies will require cell-specific targeting. Though recombinant viruses are much more efficient than nonviral vectors, the latter, especially polymers, have the advantage of being targetable via conjugation of cell-specific ligands, including sugars, peptides, and antibodies, which can be covalently attached to the polymer using a variety of chemistries. Cyclodextrin, which forms inclusion complexes with small hydrophobic molecules, has been incorporated into a gene-delivery polymer and may provide a facile and versatile attachment site for targeting ligands. Polyethylenimine (PEI) was derivatized with beta-cyclodextrin on approximately 10% of the polymer's amines (termed CD-PEI). Human insulin was also derivatized with a hydrophobic palmitate group (pal-HI), which could anchor the protein to CD-PEI/DNA polyplexes. CD-PEI was essentially nontoxic to HEK293 cells at concentrations optimal for gene delivery and mediated nearly 4-fold higher gene expression than unmodified PEI, which is relatively toxic to these cells. More importantly, addition of the pal-HI to CD-PEI enhanced gene expression by more than an order of magnitude compared to unmodified PEI, either with or without the pal-HI. Because of the relative ease with which CD-binding moieties may be attached to various types of ligands, CD-PEI may be a generally useful material for testing novel cell-specific targeting compounds.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
authors.forename: Nathan
authors.initials: N
authors.lastname: Gabrielson
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Pack
mesh_terms: D002460:Cell Line; D018014:Gene Transfer Techniques; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D011094:Polyethyleneimine; D008156:Luciferases; C031215:betadex