Kijung Kwak
Novel Bioreducible Gene Delivery Platform to Treat Parkinson's Disease
Abstract
GBA1 gene therapy targets a key genetic risk factor in Parkinson’s disease (PD) by correcting lysosomal dysfunction from GBA1 variants. Unlike current therapies focused on symptom relief, it addresses the underlying pathology. Adeno-associated virus has been used for GBA1 therapy but is mainly limited to intracranial injections due to the blood-brain barrier (BBB) and faces off-target effects, safety risks, and immunogenicity. These limitations underscore the need for systemic non-viral gene therapies with improved pharmacokinetics. We propose a strategy combining focused ultrasound (FUS)-mediated BBB opening and surface-modified bioreducible nanoparticles for systemic delivery of GBA1 plasmids to the brain. In our pilot data, the nanoparticles had strong colloidal stability, selective intracellular payload release, and high transfection efficiency. The overarching goal is to optimize the nanoparticles for enhanced delivery to the brain paired with FUS-mediated BBB opening to treat PD.
I am honored to receive the Predoctoral Fellowship in Drug Delivery from the PhRMA Foundation. This opportunity feels like a vote of confidence to pursue bold ideas and reaffirms my commitment to translating science from bench to bedside.
