(469d) Nanoscale Characterization of Self-Assembled Non-Viral Nucleic Acid Delivery Vectors

Nucleic acids can revolutionize human health outcomes, as evidenced by the mRNA vaccines used to combat COVID-19. Despite the success of these therapeutics, the physicochemical fundamental properties of the non-viral delivery vectors must be better understood to be more easily tuned and optimized. In this work, we use a blend of specialized and high-throughput experimental methods to provide a nanoscale picture of self-assembled nucleic acid therapeutics. Techniques including DLS, absorbance assays, and small-angle X-ray (SAXS) and neutron scattering (SANS) combine to assess how the storage and delivery conditions of the nanoparticles impact their structure and dynamics. The molecular interactions within the drug delivery vehicles are shown to be impacted by relevant environmental factors such as pH. Such information demonstrates what drives degradation in storage and what parameters can be changed to improve component dissociation allowing more efficient endosomal escape. Ultimately, these results can be used to optimize efficacy, enabling more flexible storage requirements, lower dosages, and improved therapeutic tolerances.