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Alexandra Piotrowski-Daspit, PhD

piotrowski-daspit-alexandra_FSGDL24
Faculty Starter Grant in Drug Delivery, 2024 University of Michigan

Antibody-Mediated Targeting Strategies to Augment Polymeric Nanoparticle Delivery to Target Tissues In Vivo

Abstract

The lungs remain a key organ of interest for the treatment of myriad diseases with gene therapy and gene editing therapeutics. As nucleic acids are rapidly cleared and do not readily cross the plasma membrane, vehicles that facilitate their delivery to cells are necessary. The primary barrier for clinical translation remains delivery to target cell types in vivo. Lipid and polymeric nanoparticles (NPs) are typically taken up by phagocytic cells of the mononuclear phagocyte system (MPS) in the liver and spleen when administered intravenously. The goal of the proposed research is to develop effective polymeric vehicles for in vivo therapeutic nucleic acid delivery to the lungs to target cell types. Biomaterials composed of poly(amine-co-esters) (PACEs) capable of conjugation to targeting moieties via maleimide chemistry will be developed. These will be assessed for biodistribution and cell-type targeting ability to the lungs using quantitative high-throughput in vivo screening tools.