Design and development of a DNA delivery system for murine dendritic cells

Dendritic cells (DC) are potent antigen presentation cells and important targets for genetic immunization. In this work two non-viral gene delivery systems using murine DC as target tissues were investigated. In the first system, a novel heptameric peptide having the sequence YTYQGKL that binds to mouse DC in a TNFα specific manner was identified by screening a phage display library. A vector consisting of a DNA binding domain and YTYQGKL was demonstrated to increase transfection efficiency when compared to the vector without YTYQGKL. In the second part, a delivery system consisting of ornithine and histidine repeats (O₁₀H₆) was found to have superior transfection efficiency than lysine based cationic peptides, which have been used widely in many laboratories. Importantly it was demonstrated that the ornithine peptide was less toxic than the lysine based peptides. Collectively, data generated from this study not only added to the growing knowledge in non-viral gene delivery but also advanced the techniques of gene manipulation of DC.