title: A pH-sensitive polymer that enhances cationic lipid-mediated gene transfer.
abstract: The efficient release of nonviral gene carriers from endosomes is an important step for the successful delivery of DNA into the cell nucleus. A synthetic pH-sensitive anionic polymer, poly(propylacrylic acid) (PPAA), was designed to aid in endosomal escape of nonviral vectors and improve the transfection efficiencies with these vectors. Transfection of NIH3T3 fibroblasts with ternary physical mixtures of the cationic lipid DOTAP, pCMVbeta plasmid DNA, and PPAA showed marked enhancement of both gene expression levels and fraction of cells transfected compared to binary control mixtures of DOTAP and DNA. PPAA also significantly improved the serum-stability of DOTAP/DNA vectors. The DOTAP/DNA/PPAA vectors maintained high levels of transfection in media containing up to 50% serum. The striking enhancement of transfection efficiency with cationic lipid/DNA/PPAA mixtures, along with the enhanced serum-stability, suggests that PPAA may provide significant improvements for the in vivo intracellular delivery of drugs such as DNA, oligonucleotides, proteins, and peptides.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Cheung
authors.forename: N
authors.initials: N
authors.lastname: Murthy
authors.forename: P S
authors.initials: PS
authors.lastname: Stayton
authors.forename: A S
authors.initials: AS
authors.lastname: Hoffman
mesh_terms: D016475:3T3 Cells; D000180:Acrylic Resins / Q000494:pharmacology*; D000818:Animals; D002412:Cations; D016503:Drug Delivery Systems; D004355:Drug Stability; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D011108:Polymers / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D014162:Transfection
chemical_list: D000180:Acrylic Resins; D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008081:Liposomes; D011108:Polymers; D000644:Quaternary Ammonium Compounds; C006903:carbopol 940; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane