BIOT 356 |
| Polyethylenimine (PEI) is one of the most widely studied polymeric gene carrier due to its superior transfection efficiency. However, its uses in vivo are limited due to high cytotoxicity and non-degradability. In this study, we ketalized PEI to achieve 1) enhanced intracellular release of nucleic acids, 2) efficient dissociation of nucleic acids from cationic polymeric backbone, and 3) lowered cytotoxicity by less attractive interactions between nucleic acids and hydrolyzed PEI. Ex vivo study showed remarkably reduced cytotoxicity of ketalized PEI and, more interestingly, transfection efficiency was found inversely proportional to molecular weight of ketalized PEI while RNA interference was observed in an opposite way. The results demonstrated that targeted delivery of plasmid DNA and siRNA to the nucleus and cytoplasm, respectively, can be achieved by appropriately modulating PEI. Characterization of the polymers, biological studies explained by a theoretical model, and implications in clinical gene therapy will be presented. |
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Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biochemical Technology |