 |
Dan Bonner Health Sciences &
Technology Grad Student |
Linear-Dendritic Block Copolymers for Targeted Gene Delivery
Many currently incurable diseases could potentially be treated using genetic vaccines. Like traditional vaccines, genetic vaccines produce an immune response to an antigen associated with a disease, which can impart prophylactic immunity on the individual. A genetic vaccine introduces a DNA plasmid that encodes for proteins expressed on a specific antigen, rather than the antigen itself, which avoids risk of infection while conferring immunity.
DNA can be delivered via viral vectors with excellent efficiency, but this technique raises safety concerns and the possibility of immune rejection. Synthetic systems, generally polymer or lipid-based, have suffered from low transfection efficiency but are largely safe and biocompatible. This project seeks to further develop a linear-dendritic block copolymer gene delivery system capable of transfecting macrophages in vitro at efficiencies on par with the best commercially available non-viral vectors. [1] This rationally designed system makes use of a cationic dendritic block to condense plasmid DNA and form complexes with favorable endosomal escape properties. The linear chain provides biocompatibility, protection from serum proteins, and can be functionalized with a targeting ligand.
[1] Wood, K.C., et al., A family of hierarchically self-assembling linear-dendritic hybrid polymers for highly efficient targeted gene delivery. Angewandte Chemie-International Edition, 2005, 44(41), 6704-6708
