“The LNPs’ lipid composition is crucial for this process, as the lipid bilayer can fuse with the cell membrane, allowing the mRNA to be directly delivered into the cells…”
The dominant and well-established mechanistic model for LNP-mediated mRNA delivery (especially for the COVID-19 mRNA vaccines) is endocytosis, followed by endosomal escape, not direct fusion at the plasma membrane.
The cationic/ionizable lipids in LNPs are designed to promote endosomal membrane disruption after cellular uptake, not fusion with the extracellular cell membrane. Direct fusion with the plasma membrane is more characteristic of viral envelopes or certain fusogenic liposomes, not the standard LNP formulations used for systemic mRNA vaccine delivery. Stating that the LNP bilayer fuses with the cell membrane oversimplifies and misrepresents the actual mechanism, which is a critical distinction in drug delivery science.