Journal
MOLECULAR THERAPY
Volume 12, Issue 1, Pages 164-170Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2005.01.021
Keywords
naked DNA vaccines; gene transfer techniques; cytotoxic T lymphocyte; adjuvants
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Funding
- NCI NIH HHS [CA 50139] Funding Source: Medline
- NIBIB NIH HHS [EB 00244] Funding Source: Medline
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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 (R-2 = 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.
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