ARMMs biogenesis pathway can be easily manipulated to deliver distinct cargo to both the plasma membrane and cytoplasm of cells.
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Summary Dr. Quan Lu has discovered a novel population of naturally secreted, non-immunogenic microvesicles that can deliver nucleic acid and protein therapeutics. Extracellular vesicles, such as exosomes, have emerged as promising candidates for drug delivery but are encountering challenges relating to their native cargo and biogenesis. Specifically, exosomes transport major histocompatibility complex (MHC) molecules that mediate immunity. Furthermore, exosomes are produced through the endolysosomal pathway that ultimately targets their cargo to the lysosome for degradation. In contrast, contents of microvesicles are delivered to the plasma membrane and cytoplasm and typically include regulatory nucleic acids and proteins involved in cell-cell communication. Dr. Lu has identified a subset of microvesicles – arrestin domain-containing protein 1-mediated microvesicles (ARMMs) – which are formed through an active, protein-mediated process that selectively controls the ARMMs’ cargo and budding mechanism. ARMMs are not predicted to transport immunogenic molecules, are relatively uniform in size, protected from degradation, and are predicted to avoid the endosomal pathway. Research from the Dr. Lu lab has demonstrated that the ARMMs biogenesis pathway can be easily manipulated to deliver distinct cargo to both the plasma membrane and cytoplasm of cells.