New lipid nanoparticle delivers capped circular RNA for longer-lasting gene expression

Researchers at Nagoya University in Japan have developed a groundbreaking method for delivering circular RNA (cirRNA) into cells, leading to longer-lasting gene expression. This innovation, published in Cell Biomaterials, holds promise for creating more effective mRNA-based therapeutics, such as cancer vaccines and GLP-1 treatments for obesity.

Lipid nanoparticles (LNP) have proven successful in delivering mRNA strands to cells, enabling the production of crucial proteins like those found in COVID-19 vaccines. However, the stability of mRNA is compromised by degradation enzymes in cells, leading to a shorter duration of gene expression. Circular RNA, on the other hand, lacks a start or stop point, making it less susceptible to degradation.

Scientists at Nagoya University, in collaboration with FUJIFILM, addressed this challenge by creating a modified circular RNA called Cap-cirRNA. This version incorporates a cap end, combining the stability of cirRNA with the efficient translation capabilities of mRNA. To transport both linear mRNA and Cap-cirRNA into cells, researchers utilized a new lipid nanoparticle called FL0445-LNP, developed by FUJIFILM Corporation.

FL0445-LNP, with its branched biodegradable chains, offers enhanced flexibility compared to conventional LNPs. In their experiments, the researchers demonstrated a 10-fold increase in mRNA activity using FL0445-LNP, alongside minimal inflammatory response. The team successfully administered both linear mRNA and Cap-cirRNA in mice, showing that Cap-cirRNA provided greater functional activity.

This breakthrough technology could revolutionize drug development, offering extended treatment durations and reducing the need for multiple injections. Potential applications include cancer vaccines, genome editing, and protein supplements for genetic disorders.