“Designing polymeric nanoparticles for systemic delivery in vivo to enhance therapeutic effects in key tissues”
The primary barrier for clinical translation of nanomedicines remains delivery to target tissues in vivo. In this seminar, I will describe our work on developing polymeric nanoparticles (NPs) to deliver therapeutic nucleic acids to a variety of tissues following systemic intravenous administration, with a focus on peptide nucleic acid (PNA)-based gene editing therapeutics in cystic fibrosis and β-thalassemia disease contexts. These monogenic disorders are attractive targets for gene editing and can be corrected using non-nuclease-based PNA gene editing agents. PNAs designed to bind specific sites in genomic DNA can initiate an endogenous DNA repair response and site-specific modification of the genome when “donor DNA” templates containing a desired sequence modification are co-delivered using polymeric vehicles. In recent work, we have found that gene editing efficiency can be significantly enhanced using a new class of polymeric vehicles consisting of poly(amine-co-ester) (PACE) polymers designed for safe and effective nucleic acid delivery. To close the talk, I will describe a robust high-throughput quantitative microscopy-based platform to standardize and accelerate the analysis of circulation half-life of nanomedicines to facilitate pre-clinical screening in vivo. This tool, alongside the development of novel polymeric carriers, can be used to study the structure-function relationships that guide the physiological fate of NPs in order to rationally design more effective delivery vehicles for future applications.