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The term refers to the collective cellular structures and pathways responsible for the internalization of therapeutic agents, particularly lipid nanoparticles (LNPs) and nucleic acid-based drugs. This is not a single molecular entity but a complex system involving the lipid bilayer and various proteins involved in endocytic routes such as macropinocytosis, clathrin-mediated endocytosis, and caveolae-mediated endocytosis (Sahin et al., 2020, Nature Reviews Drug Discovery). In the context of mRNA vaccines, myocytes at the injection site and professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, utilize this machinery to engulf the delivery vehicle. Once internalized, the cargo must achieve endosomal escape to reach the cytosol for translation into functional proteins (Pardi et al., 2018, Nature Reviews Drug Discovery). This process is critical for the pharmacokinetics and pharmacodynamics of modern genetic medicines, as it dictates the efficiency of antigen production and the subsequent activation of the adaptive immune system.
Endocytosis-mediated cellular uptake followed by endosomal escape and cytosolic delivery of cargo.
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See how Gosset can support your research on Cell membranes and endocytic machinery of antigen-presenting cells and myocytes.