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mRNA-based protein replacement therapy has become one of the most widely applied forms of mRNA therapy, with lipid nanoparticles (LNPs) being extensively studied as efficient delivery platforms for mRNA. However, existing LNPs tend to accumulate in the liver or kidneys after intravenous injection, highlighting the need to develop vectors capable of targeting specific organs. In this study, we synthesized a small library of ionizable lipids and identified PPz-2R as a promising candidate, exhibiting lung-targeting capabilities, high mRNA transfection efficiency, and good stability through structure-activity relationship studies.
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