Research Results from a Collaboration Between Satoshi Uchida, Professor at Tokyo University of Science, and iCONM Published in *ACS Nano*
Since the administration of COVID-19 mRNA vaccines began worldwide, various countries have been exploring the use of mRNA for therapeutic purposes. To protect the mRNA and deliver it to organs such as the spleen, it is typically encapsulated in LNPs (lipid nanoparticles) before administration. However, it is known that these LNPs accumulate in the liver, where they can induce protein expression or cause hepatitis.
In this study, we focused on the “hepatic sinusoids”—capillaries that remove foreign substances from blood flowing into the liver and excrete them into bile. We hypothesized that the accumulation of LNPs (which carry a positive charge) in the liver is caused by their adsorption to the negatively charged barrier of the hepatic sinusoid walls. Based on this, we developed a coating agent for the hepatic sinusoid walls by attaching two molecules of polyethylene glycol to positively charged amino acid polymers, such as ornithine. Animal experiments using mice confirmed that when this coating agent was administered to temporarily neutralize the negative charge on the hepatic sinusoid walls, followed by administration of mRNA-loaded LNPs, no accumulation in the liver was observed, and therapeutic effects were achieved with a lower dose. Applications for infectious disease prevention vaccines, cancer treatment vaccines, and cancer cytokine therapy have also been evaluated, and in all cases, the intended treatment was achieved with high safety and efficacy.
https://change.kawasaki-net.ne.jp/en/project/performance/1220
