This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Researchers at Nagoya University in Japan in collaboration with FUJIFILM have developed a novel way of delivering circular RNA (cirRNA) into cells, paving the way for longer-lasting mRNA-based therapeutics including cancer vaccines and GLP-1 obesity treatments. The research is published in Cell Biomaterials.
A crucial part of the success of mRNA vaccines in combating the COVID-19 pandemic was finding a way to insert delicate mRNA strands into our cells. The answer was a class of molecular vehicles called lipid nanoparticles (LNP). These microscopic fat bubbles encased mRNA strands, allowing our cells to take them in.
Once inside, the LNPs released mRNA, which cells translated into SARS-CoV-2 spike proteins, triggering an immune response that helped prepare our defenses against the virus. Linear mRNA strands carry a cap end and a tail end, which guide ribosomes to initiate the translation of genes into proteins. But degradation enzymes within the cell can also use the same terminal points to attack and break down the mRNA. cirRNA, being a loop, does not have a start or endpoint.
It is thus more resistant to degradation. Additionally, without a specific "stop" marker, ribosomes can keep riding this loop to code for proteins. This makes cirRNA capable of driving gene expression for longer periods.
On the other hand, cirRNA relies on internal instructions within its loop for gene translation. As a result, its gene expression efficacy can be lower compared with mRNA's cap and end marker system. To counter this, Hiroshi Abe, Seigo Kimura and their team at Nagoya University's Integrated Research Consortium on Chemical Sciences (IRCCS) and the Department of Chemistry perfected making a cirRNA with a cap end.
Called Cap-cirRNA, it "combines the strengths of mRNA and cirRNA to provide durability and efficient (gene) translation for a longer time," Abe explains. Next, Abe and his team needed a delivery vehicle that could transport both linear mRNA and their Cap-cirRNA into a cell. For this, they obtained a new lipid nanoparticle called FL0445-LNP from researchers at the Bioscience & Engineering Laboratories at FUJIFILM Corporation.
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