EXPLORING CARRIER IMPACT ON IMMUNE RESPONSE TO NUCLEIC ACID NANOPARTICLES AND PROVIDING INSIGHTS INTO CONDITIONALLY ACTIVATED THERAPEUTIC NUCLEIC ACIDS

In this work, the in vitro characterization profiles of delivery vehicles, specifically polyamidoamine (PAMAM) dendrimers, are assessed to investigate their impact on pre-established immune responses to immunostimulatory and immunoquiescent nucleic acid nanoparticles (NANPs). Isolated human peripheral blood mononuclear cells (PBMCs) were used as the universal model system for these investigations, providing detailed understanding of the impact delivery vehicles play on NANP recognition. Additionally, to further identify mechanisms of immune recognition of these novel formulations, several engineered reporter cell lines were employed to understand the involvement of pattern recognition receptors, relevant to nucleic acid detections in human cells.
Furthermore, we explore the design and in vitro assessment of conditionally activated reconfigurable nucleic acid nanoparticles (recNANPs). By further investigating dynamic recNANPs and their interactions with delivery vehicles and the immune system, we aim to gain deeper insights into these systems. This innovative platform will enable the development of refined design principles for therapeutic systems incorporating NANPs, allowing for the creation of more precise and optimized options.