Since the COVID-19 pandemic, ionizable lipids have gained significant attention for gene delivery in gene editing and enzyme replacement therapy. However, most available ionizable lipids were developed for vaccines and optimized for immunogenicity, which limits their suitability for repeated systemic dosing. We present the rational design of biodegradable ionizable lipids that offer improved tolerability and reduced organ/immune toxicity while maintaining robust mRNA expression. Our proprietary lipids exhibit high circulatory stability and degrade selectively upon intracellular stimulation, enabling favorable safety and clearance profiles. This work demonstrates hepatic- and spleen-targeted LNP formulations with potential applications in infectious disease vaccines and repeated-dose mRNA therapeutics. These formulations address key challenges in non-viral RNA therapeutic delivery.
Yuhei Onizuka, Research Scientist, Life Science Research Laboratory, NOF CORPORATION
