| Gene delivery to neurons has the potential to make a significant impact on the treatment of central nervous system diseases. The delivery of transgenes that encode proteins that can promote the division, survival, and migration of new neurons is a promising approach to mitigate neurodegeneration that is observed in these diseases. This work describes the development of a synthetic, polymer-based delivery vehicle that incorporates peptides to mediate intracellular trafficking to neurons. Chapter 1 introduces the gene delivery field, describing the most common vectors that are employed and the progress of their development for clinical use. In Chapter 2, a targeting peptide is evaluated for its ability to transfect specific cell-types after delivery to the mouse brain. In Chapter 3, a novel membrane-active peptide is employed to improve the efficiency of vehicles by mediating endosomal escape and a shortened sequence is investigated in Chapter 4. The targeting peptide and endosomal escape peptide are incorporated in a single vehicle and evaluated for in vitro transfection efficiency in Chapter 5 and for in vivo transfection efficiency in Chapter 6. |
