Optimization of ionizable lipid nanoparticle formulations for plasmid DNA delivery in neurons

Gene therapy is a promising approach to be applied in neurological disorders, such as enhancing neural regeneration after brain injury and gene correcting for inherited or acquired neurodegenerative conditions. An obstacle in this field is the effective delivery of therapeutic genes to targeted cells. Ionizable lipid nanoparticles (LNPs) are widely employed as vectors for delivering nucleic acids due to their excellent safety profile and high efficacy. These LNPs are specifically designed to encapsulate nucleic acids, protecting them from degradation, and facilitate their transportation within cells. In this study, we designed a mini library of LNPs encapsulating plasmid DNA (pDNA) to improve transfection efficiency in neurons.