Developing Gene Editing Therapeutics, Biodegradable Polymeric Delivery Vehicles, and High-throughput Platforms for the Treatment of Cystic Fibrosis- Supplement

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY Cystic fibrosis (CF) is a progressive genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to lung and gastrointestinal (GI) tract dysfunction. There is an urgent unmet need for treatments for people with CF (pwCF) that have rare CFTR variants (~10% of pwCF) and are either not eligible for, or do not respond to, highly effective modulator therapies (HEMTs). Despite advances in gene editing technology and other nucleic acid therapeutics, in vivo delivery to target tissues remains a primary barrier to clinical translation. The goal of the proposed research is to develop high-throughput technologies for identifying effective vehicles for in vivo therapeutic nucleic acid delivery for the treatment of CF. In Aim 1, novel poly(amine-co-ester) (PACE) polymeric materials that are biodegradable and biocompatible will be developed for in vivo delivery of nucleic acid-based therapeutics to the lungs and assessed using high- throughput in vivo platforms to determine the structure-function relationships guiding physiological fate. In Aim 2, physiologically relevant 3D culture models will be developed as high-throughput screening tools to assess delivery and efficacy of CF therapies. Overall, the proposed interdisciplinary research is highly clinically relevant, furthering the translation of promising gene editing/nucleic acid therapeutics for CF and other genetic diseases. Dr. Piotrowski-Daspit received her Ph.D. in Chemical and Biological Engineering and is currently an Assistant Professor of Biomedical Engineering and Internal Medicine – Pulmonary and Critical Care Medicine Division at the University of Michigan. She has been a faculty member since February 2023. She has been developing polymeric NPs for nucleic acid delivery and high-throughput in vivo tools. The training Dr. Piotrowski- Daspit received during the K99 phase of this award acquired enabled her to gain significant experience in therapeutic development for CF and integrate her into the CF research community. This experience, together with her background in biomedical engineering, biomaterials and drug delivery, has placed her among a select group of scientists with the skills and breadth of knowledge necessary to effectively pursue interdisciplinary work on nucleic acid delivery and editing of genetic disorders in this R00 phase of the award.