Nagoya University and Fujifilm Develop Lipid Nanoparticle That Boosts Circular RNA Delivery Tenfold

Nagoya University and Fujifilm Corporation have jointly developed a novel lipid nanoparticle (LNP) that, for the first time, enables efficient delivery of capped circular RNA into animals. The findings were published in the journal Cell Biomaterials on August 20.

Experimental data show that this LNP improves the delivery efficiency of model mRNA by more than tenfold and that of capped circular RNA by over twofold, while eliciting a relatively low inflammatory response. In obese model mice, the team tested capped circular RNA encoding GLP-1 and observed better blood sugar control compared with linear mRNA formulations.

Because capped circular RNA lacks free ends and incorporates a cap structure, it is more resistant to degradation and can sustain protein production over a longer period. This primarily addresses the short duration of action and the need for repeated administration in RNA therapies.

The technology is based on the branched ionizable lipid FL0445 provided by Fujifilm. Compared with conventional LNP formulations, it offers higher delivery efficiency and better compatibility with the relatively rigid structure of circular RNA. Gene expression analysis in mouse liver and spleen showed that FL0445-LNP induced markedly lower immune and inflammatory responses than existing formulations.

The research team noted that intravenously administered LNPs currently mainly target the liver, and delivery efficiency to other organs or tissues still requires improvement. The production process for circular RNA, including purity control and scalable manufacturing, has also not been fully resolved.

The study remains at the preclinical stage in mice, and efficacy and safety in humans have not yet been verified. The team conducted glucose tolerance tests in obese model mice, but long-term body weight changes, long-term blood sugar control, and safety under chronic dosing conditions still require further experiments. Potential applications include metabolic diseases and vaccines, but the technology remains far from clinical use.