pH-responsive polymers for nucleic acid and vaccine delivery

Abstract

Biomacromolecules such as nucleic acids and peptides have great potential as therapeutics but must overcome many challenging biological barriers to succeed in the clinic. In this work, we present several investigations of stimulus-responsive polymers developed to navigate both extracellular and intracellular barriers to biologic drug delivery. We begin with a review of past applications of pH-responsive chemistries in nucleic acid delivery (Chapter 1). After screening a panel of lytic peptides in a pH-sensitive polymer conjugate system that mediates endosomal escape of plasmid cargo (Chapter 2), we evaluate the most promising gene delivery vector in a mouse model of traumatic brain injury (Chapter 3). Our efforts to develop engineered stem cells transplants as alternatives to gene delivery are then discussed (Chapter 4). Finally, we adapt our pH-responsive polymer for the delivery of peptide vaccine cargo (Chapter 5) and detail future directions to further improve antigen and adjuvant delivery with polymers (Chapter 6).