Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells

At a dose of 1 mg/kg siRNA in mice, LNPs with ALC-0315 achieved a 2- and 10-fold greater knockdown of coagulation factor VII and ADAMTS13, respectively, compared to LNPs with MC3.

• LNPs containing ALC-0315 are more effective than those with MC3 for delivering RNA to hepatocytes and hepatic stellate cells.
• A high dose of ALC-0315 LNPs (5 mg/kg) is associated with increased markers of liver toxicity, such as ALT and bile acids.
• In contrast, the same high dose of MC3 LNPs does not show increased liver toxicity markers.
• The findings suggest that while ALC-0315 provides potent knockdown of target proteins, it may carry a risk of hepatotoxicity at higher doses.

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