Dendrimer-based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I

摘要

5A2-SC8 mDLNPs delivered FAH mRNA to normalize body mass and liver function and extend survival in FAH"' knockout mice suffering from HT-1. We found that LNPs optimized for mRNA delivery should contain significantly less ionizable cationic lipid and more zwitterionic phospholipids compared to standard siRNA formulations. This provides a rational design guideline to redevelop other siRNA-delivering LNPs for delivery of mRNA. Moreover, the capability of 5A2-SC8 mDLNPs to deliver FAH mRNA to diseased livers without any carrier toxicity makes this system suitable for treatment of a wide variety of liver diseases.