On Oct 10th, research team from RinuaGene Biotechnology Co. Ltd and Chinese Academy of Medical Sciences and Peking Union Medical College published a groundbreaking research paper titled "Discovery of Ketal-Ester Ionizable Lipid Nanoparticle with Reduced Hepatotoxicity, Enhanced Spleen Tropism for mRNA Vaccine Delivery" in the journal "Advanced Science" (impact factor: 15.1).
In the quest to advance mRNA vaccine development, the safety and efficacy of lipid nanoparticle (LNP) delivery systems stand as pivotal factors. Researchers shine a spotlight on a new series of ketal ester lipids (KELs) that promise to reshape the landscape of mRNA vaccine delivery.
These KELs are engineered with a biodegradable ketal moiety in the linker and ester segments in the tail. Through rigorous iterative optimization, the researchers meticulously tuned the head and tail groups of these lipids to adjust their pKa and molecular shapes, identifying (4S)-KEL12 as a standout ionizable lipid for mRNA delivery.
(4S)-KEL12 LNPs outperformed the established DLin-MC3-DMA LNPs, delivering significantly higher efficacy and lower toxicity. When compared to SM-102 LNPs, (4S)-KEL12 LNPs exhibited superior spleen tropism, reduced liver tropism, and less hepatotoxicity. Moreover, these LNPs demonstrated impressive biodegradability following intramuscular or intravenous injection.
One of the most exciting findings was the robust cellular immune response elicited by (4S)-KEL12 LNPs encapsulated with a therapeutic mRNA cancer vaccine. This resulted in significant tumor regression and extended survival in tumor-bearing mice, underscoring the therapeutic potential of these LNPs.
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