Presentation at the Industry Technology Symposium of the 11th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan: “ Development of novel DDS polymers and potential for non-hepatic delivery ”

We gave a presentation at the Industry Technology Symposium of the 11th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan, held at Dejima Messe Nagasaki from July 7th to 9th, and are pleased to introduce the content of our presentation.

Presentation

Presentation Overview

Drug delivery system (DDS) is an essential technology for nucleic acid drugs, and one of the main technologies is lipid nanoparticles (LNPs). In LNP formulations, polyethylene glycol (PEG) modifications are often performed on the LNP surface to prevent aggregation during manufacturing and to improve blood retention during intravenous administration. However, recent studies have demonstrated that antibodies against PEG are generated, and concerns about reduced drug efficacy because of enhanced blood clearance and sensitivity to PEG have been pointed out.　Nippon Shokubai has been developing PGLMMA as a next-generation DDS polymer that can dispel these concerns. The particles modified with this polymer did not produce antibodies in the administration test to mice, and the decrease in blood retention during multiple doses was suppressed.　In addition, hydrophilic polymer-modified particles are said to be difficult to enter cells, but PGLMMA-modified LNPs showed significant cellular uptake.　Our investigation into the cell uptake mechanism of LNPs showed that some particles interact with cell surface transporters. Furthermore, in vivo mRNA-LNP expression assays demonstrated that some composition decreased hepatic accumulation while enhancing accumulation in the spleen. In this presentation, we also introduced the latest in vivo test results.

Meeting Information