Self-assembled synthetic polymer complexes for delivery of immunomodulatory nucleic acids

Abstract

Biomaterials that provide precision control over immune function could enable next generation vaccines and immunotherapies for infectious diseases, cancer, and autoimmune diseases. Rational design of biomaterial delivery vehicles allows use of conventional benefits of drug delivery vehicles – for example co-delivery, controlled release, and targeting – and newly discovered immunomodulatory effects that arise from the physicochemical features of delivery vehicles. This thesis investigates the intrinsic ability of poly(ß-amino esters) to stimulate immune cells in both soluble and nanoparticle form. Further, it examines the intrinsic stimulatory capacity of rationally designed self-assembled RNA nanostructures delivered to immune cells in soluble form and when complexed with poly(ß-amino esters) to enhance immune stimulation. These studies take advantage of two models of innate immunity using primary mouse dendritic cells and a macrophage cell line to characterize immune response. Knowledge linking physicochemical features of these formulations to inflammatory mechanisms could support more rational design approaches for vaccines and immunotherapies.