Beta-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization.
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.
Greenland
John R
JR
Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, MA 02215, USA.
Liu
Huining
H
Berry
David
D
Anderson
Daniel G
DG
Kim
Woong-Ki
WK
Irvine
Darrell J
DJ
Langer
Robert
R
Letvin
Norman L
NL
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
D000941:Antigens; C113154:CRL 1005; D011108:Polymers; D019444:Vaccines, DNA; D001616:beta-Galactosidase