title: Beta-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization.
abstract: Increased in vivo expression of intramuscularly delivered plasmid DNA will be essential for clinical success in gene therapy and plasmid DNA vaccination. We screened polymers from a library of beta-amino esters for their ability to augment transgene expression as measured by beta-galactosidase activity and cellular immune responses. Among the candidates identified in this screen, poly[(1,6-di(acryloxyethoxy)hexane)-co-(4-aminobutanol)] enhanced plasmid DNA transgene expression by sevenfold (P=0.0001) and its immunogenicity by 70% (P=0.03). We found that polymers with moderately hydrophobic backbones and terminal alcohol groups facilitated transfection most effectively in vivo. We also observed a log-linear correlation (R2=0.93) between peak cellular immune responses and transgene activity in all evaluated polymer-plasmid DNA formulations, clarifying the relationship between immunogenicity and the quantity of expressed antigen.
authors.affiliation: Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Greenland
authors.forename: Huining
authors.initials: H
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Berry
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Woong-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D007111:Immunity, Cellular; D051379:Mice; D009132:Muscles / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D011108:Polymers; D013997:Time Factors; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; C113154:CRL 1005; D011108:Polymers; D019444:Vaccines, DNA; D001616:beta-Galactosidase