Exploring the Interface Between Therapeutically Relevant Polymers and the Immune System

Abstract

In order to ameliorate current maladies, improvements to medicaments and treatment regimens are required. Our lab seeks to translate findings from the laboratory bench to the patient bedside using two approaches: 1) the development of RNA aptamers that bind with high affinity and specificity to defined molecular targets, and 2) repurposing cationic binding polymers as anti-inflammatory agents. This dissertation herein, discusses both of these approaches and summarizes the findings obtained during my graduate training. In the first study, I illustrate how anti-PEG antibodies are capable of binding to and inhibiting a therapeutic RNA aptamer as demonstrated by reduction in drug potency in vitro and in vivo. In the second portion, the development of novel cationic polymer derivatives is discussed, which will help us to determine nucleic acid binding polymer mediated anti-inflammatory mechanisms of action. These findings shed light on the importance of careful and considered drug design to inform the development of future therapeutics. Despite the advances in translational research, there remains a paucity in our understanding of how drugs impact the immune system and this dissertation, in toto, seeks to aid in the development of improved bona fide therapies.