Abstract:
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 b-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.
Bio:
Dr. Alexandra S. Piotrowski-Daspit, Ph.D. is a Postdoctoral Fellow in the Biomedical Engineering Department at Yale University. Alexandra received her bachelor's degree in Chemical-Biological Engineering and Biology from the Massachusetts Institute of Technology (MIT) in 2011 and her Ph.D. in Chemical & Biological Engineering from Princeton University in 2016, where she worked in the laboratory of Professor Celeste Nelson on developing three-dimensional cell culture models to study cell behavior during development and disease processes. At Yale, she works on a highly interdisciplinary team under the mentorship of Professors W. Mark Saltzman, Peter Glazer, and Marie Egan, focusing on developing polymeric vehicles for the delivery of a variety of therapeutic nucleic acids.

Dr. Piotrowski-Daspit’s main project involves synthesizing novel biodegradable polymers and formulating them into vehicles to deliver peptide nucleic acid (PNA)-based gene editing therapeutics for the treatment of hereditary diseases such as Cystic Fibrosis. She has received funding from the NIH (NHLBI K99/R00 Pathway to Independence Award) and the Cystic Fibrosis Foundation (Postdoc-to-Faculty Transition Award) to support her interdisciplinary research in chemical/biomedical engineering, biomaterials, genetics, and drug delivery to develop therapeutic strategies to treat hereditary disorders with a focus on lung diseases.

Zoom Link: https://umich.zoom.us/j/96508834308