Cationic polymers are used widely as condensing agents for the delivery of DNA. However, the intracellular release, or 'unpackaging', of DNA from a cationic polymer to which it is bound presents a challenging problem from a design perspective because it requires the introduction of functionality that inherently opposes that required for efficient DNA condensation. The release of DNA from electrostatically self-assembled polycation/DNA complexes is a critical and poorly understood step in the non-viral gene delivery process and creates opportunities for the design of new materials that balance these design criteria effectively. We are developing synthetic cationic polymers that undergo controlled reductions in cationic charge density via side-chain hydrolysis to promote the dissociation of electrostatically bound DNA under physiological conditions. These cationic polymers form self-assembled complexes with plasmid DNA at physiological pH and release the DNA over time frames that are meaningful in the context of gene delivery. Using this approach, it is possible to exert control over the rates (e.g., from hours to days) at which DNA is released from these materials. The continued development of synthetic materials that provide control over the self-assembly and dissociation of polycations with DNA will address a problem of fundamental biophysical interest and could contribute to a more complete understanding of the factors that limit non-viral gene delivery. These materials could also find use in other biotechnical applications for which control over the association and release of DNA from synthetic materials is required.