Lipid nanoparticles (LNPs) have become established non-viral delivery systems for transient mRNA expression. However, certain gene and cell therapy applications may benefit from a longer yet still transient expression profile. In this work presented at ASGCT 2026, Minicircle DNA was evaluated as a DNA cargo for SM-102-based lipid nanoparticles in HEK293 cells.
The study demonstrated that Minicircle DNA delivered by SM-102 LNPs resulted in prolonged transient reporter gene expression compared to both conventional plasmid DNA and mRNA formulations. Peak transfection efficiency was observed three days after transfection, with Minicircle DNA achieving substantially higher expression levels than plasmids while maintaining detectable expression over an extended time period. In contrast, mRNA-mediated expression decreased rapidly within the first 48 hours.
These findings support the expanding role of backbone-free Minicircle DNA in non-viral delivery workflows requiring sustained but non-integrating transient expression. Potential applications range from ex vivo cell engineering to next-generation therapeutic strategies already being explored in clinical development.