Key result
Lipid nanoparticle helper and ionizable lipids dictate liver tropism and efficacy via ApoE-dependent and LDLR-independent mechanisms.
The composition of helper and ionizable lipids in mRNA LNPs is crucial for ApoE-mediated liver tropism and determines the pathway of cellular uptake.
Potent Liver-Tropic mRNA Lipid Nanoparticles Helper and ionizable lipids play a crucial role in determining apolipoprotein E (ApoE) binding and subsequent liver tropism and low-density lipoprotein receptor (LDLR) mediated uptake. Ionizable lipids primarily govern the LDLR-independent uptake pathway. This complementary interplay between lipid components ultimately governs LNP delivery performance and therapeutic efficacy in the liver. More details can be found in the Research Article by Ashish Sarode, Shrirang Karve, and co-workers (DOI: 10.1002/adma.202517893).
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Sarode et al. (2026) studied this question. Liver-Tropic mRNA Lipid Nanoparticles was evaluated. Helper and ionizable lipids in mRNA lipid nanoparticles govern ApoE binding, liver tropism, and LDLR-independent uptake, determining delivery performance and therapeutic efficacy in the liver.
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