This lecture will center on new functional cationic, zwitterionic, and mixed cationic/zwitterionic polymers and their use in gene therapy applications. In the context of non-viral methods for transfection, we seek to synthesize polymers that bring beneficial elements to all of the key areas of gene delivery, including protection of DNA from degradative elements, promoting cell and nuclear entry of DNA, and enabling release of DNA for its entry into the protein expression process. Specifically, a ring-opening methathesis polymerization platform was developed as a modular approach to comb-type polymer synthesis, and the integration of oligopeptides intended to complex DNA through electrostatic binding, promote DNA nuclear entry through selection of oligopeptide sequence, and facilitiate DNA release through architectural and/or functional group selection. In muscle cells and numerous cancer cell lines, this polymer platform outperforms the commercially available transfection reagents, both in vitro and in vivo, holding promise for future new and improved therapeutic approaches to gene-based diseases.