Adding a polyamine to lipid nanoparticles improves safe delivery of genetic material into cells

The p-LNP platform achieved up to a 100-fold increase in luciferase bioluminescence expression in the liver.

• Incorporating 4.5 mol% of a specific polymer (NS102) into lipid nanoparticles enhanced their ability to deliver RNA.
• The polymer's molecular weight and amine composition were found to significantly affect delivery performance and compatibility.
• The modified lipid nanoparticles improved pH-buffering capacity, endosomal escape, and RNA stability.
• Increased mRNA transfection efficiency and siRNA activity were observed in mouse models after both intravenous and intramuscular administration.
• The effective dose of siRNA against factor VII produced by the liver was reduced by 50% compared to standard lipid nanoparticles.
• No significant cytotoxicity or liver toxicity was observed in mice, indicating good biocompatibility of the p-LNP formulations.

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