Researchers at Nagoya University in Japan, in collaboration with FUJIFILM Corporation, have developed a lipid nanoparticle (LNP) designed to deliver circular RNA (cirRNA) into cells. The approach could support development of longer-lasting mRNA-based therapeutics, including cancer vaccines and treatments that use glucagon-like peptide-1 (GLP-1).
The study was published online August 19 in Cell Biomaterials.
LNPs were critical to the development of mRNA vaccines against COVID-19 because they can encapsulate and transport fragile mRNA into cells. However, conventional linear mRNA can be degraded by enzymes that attack its terminal ends.
A delivery system for durable RNA
Unlike linear mRNA, cirRNA forms a continuous loop without a defined start or end, making it more resistant to degradation. Its structure can also allow ribosomes to continue producing proteins from the RNA. However, cirRNA can have lower gene-expression efficiency because it relies on internal instructions to initiate translation.
To address this limitation, Hiroshi Abe, Seigo Kimura, and colleagues at Nagoya University developed Cap-cirRNA, a circular RNA incorporating a cap end. In a recent press release, Abe said the technology “combines the strengths of mRNA and cirRNA to provide durability and efficient (gene) translation for a longer time.”
The researchers then used FL0445-LNP, a lipid nanoparticle developed by researchers at FUJIFILM Corporation’s Bioscience & Engineering Laboratories. According to the researchers, the nanoparticle contains branched biodegradable lipid chains rather than the linear chains used in conventional LNPs. This architecture provides greater internal flexibility and enables the particle to carry nucleic acids with different sizes and structures.
The researchers reported that FL0445-LNP produced a 10-fold increase in mRNA activity compared with conventional LNPs while causing a negligible inflammatory response.
“Once you have figured out a common way to safely deliver stronger or more durable mRNA, then that opens up many more possibilities,” said Kimura, assistant professor at Nagoya University and lead author of the study.
Newly developed lipid nanoparticle FL0445-LNP’s branched structure can carry both mRNA, and more durable Cap-cirRNA therapeutics while generating lower inflammatory response when administered in mice.
Testing the platform in mice
The team tested FL0445-LNP delivery of both linear mRNA and Cap-cirRNA encoding GLP-1 in mice. Both approaches successfully produced GLP-1 in vivo, while Cap-cirRNA demonstrated higher functional activity. Further research is needed to optimize the technology.
The researchers also identified potential applications in cancer vaccines, genome editing, and protein-based treatments for genetic disorders.
Note: This news summary was generated by AI based on a published press release, followed by a review from human editors.
