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May 15, 2025 – May 19, 2025
Chih-Chun (Roger) Chang, Pharmsci graduate student (Mecozzi Research Group), will be defending his PhD research thesis:
Development of lipid-based mRNA delivery systems and fluorous probes for immune cell engineering and labeling
Abstract:
Due to their physicochemical characteristics, immune cell engineering and labeling can be achieved using lipid-based delivery systems. The delivery systems can be designed to carry and deliver genetic cargo to immune cells, thereby enabling immune cells to gain therapeutic functions. Among non-viral immune cell engineering methods, lipid-based mRNA delivery systems have been extensively explored due to the high transfection efficiency of mRNA lipid nanoparticles (LNPs) in various hard-to-transfect primary cells. In this thesis, we developed an LNP formulation using FDA-approved lipids to deliver mRNA encoding an anti-GD2 chimeric antigen receptor (CAR) to human primary T cells and NK cells. High expression levels and favorable kinetics of fluorescent reporter proteins were observed in both cell types after mRNA LNP transfection. The CAR immune cells generated using LNPs could kill the target cancer cells in vitro and secrete cytotoxic cytokines. A methodology study of freeze-thawed mRNA NK cells reveals cryopreservation as a critical step for stocking the allogeneic cell therapeutic, potentially limiting an off-the-shelf strategy to current clinical protocols.
Besides immune cell engineering, lipid-based delivery systems are widely used in immune cell labeling. Herein, MRI-based fluorous probes have been designed based on lipid formulations. To improve the 19F MR sensitivity of perfluoro-15-crown-5-ether (PFCE) nanoemulsion, extremely small-sized iron oxide nanoparticles (ESIONs) were adopted as a potential T1-shortening agent. Several catechol ligands with fluorinated moieties were synthesized as anchor groups with high affinity towards paramagnetic ferric ions and screened to make fluorous ESIONs via ligand exchange. Fluorous ESIONs are highly fluorophilic and soluble in a fluorous phase, giving the potential to be used in future theranostic formulations.
- The defense will be hosted in a hybrid format. Free donuts and coffee will be provided
- The oral presentation will mainly focus on the immune cell engineering research.
