(109a) Invited Speaker: Design of Synthetic Materials for Spatial, Temporal, and Active Control Over Nucleic Acid Delivery: Surface-Mediated and Redox-Based Approaches

The ability to deliver nucleic acids to cells and tissues exactly when and where they are needed is critical in a broad range of fundamental and applied contexts, ranging from the development of new tools for biotechnology and biomedical research to the development of new therapies and more effective clinical interventions. This presentation will focus on the design of synthetic soft materials that can be used to provide spatial, temporal, and/or external (user-defined) control over the delivery of DNA and siRNA to cells in two different contexts. The first part of the presentation will provide an overview of our recent work on the design and fabrication of ultrathin and erodible polymer-based thin films (polyelectrolyte multilayers) that promote the localized release of DNA from surfaces, with a focus on (i) fundamental aspects of design and assembly that can be used to provide spatial and temporal control over erosion and release, and (ii) the ability of these ultrathin coatings to release or locally transfer therapeutic plasmid DNA constructs from the surfaces of interventional devices and promote beneficial physiological responses in vivo. The second part of the presentation will focus on the design of ferrocene-containing cationic lipids that provide redox-based control over the extent to which DNA and siRNA is (or is not) internalized by cells. The unique properties of these redox-active lipids can be exploited to design ‘inactive’ or dormant lipoplexes that do not enter cells, but that can be transformed into active lipoplexes that promote high levels of transfection or gene silencing by the simple extracellular addition of soluble or solid-phase reducing agents. This redox-based approach thus provides new principles for the active chemical transformation, external and remote activation, and spatial patterning of transgene expression in ways that are difficult to achieve using conventional cationic lipids.