1.F.4.  The Extracellular Vesicle Cargo Delivery (EVCD) Family 

Extracellular vesicle (EV) horizontal line (including exosomes and the microvesicles horizontal line) are involved in cell-cell communication. EVs encapsulate different types of molecules such as proteins or nucleotides and are long-lasting contenders for the establishment of personalized drug delivery systems. The intrinsic capacities for uptake and cargo delivery of basic EVs might be too limited to serve as a potent delivery system. Bui et al. 2023 developed two synergistic methods to, respectively, control EV cargo loading, and enhance EV cargo delivery through fusion without a requirement for a viral fusogenic protein. Briefly, cargo loading is enabled through a reversible drug-inducible system that triggers the interaction between a cargo of interest and CD63 (see 8.A.63.1.19), a well-established transmembrane EV marker. Enhanced cargo delivery is promoted by overexpressing Syncytin-1, an endogenous retrovirus envelop protein with fusogenic properties encoded within the human genome (see TC# 1.G.9.1.1). The authors utilize this method to develop highly potent killer EVs, which contain a lethal toxin responsible for protein translation arrest and acceptor cell death. These advanced methods and future downstream applications may open promising doors in the manufacture of virus-free EV-based delivery systems (Bui et al. 2023). For example, human blastocysts take up extracellular vesicles secreted by endometrial cells containing miRNAs related to implantation (Segura-Benítez et al. 2023).  Extracellular vesicle formation provides a copper-secretion mechanism in Gram-negative bacteria (Lima et al. 2022).  Extracellular vesicle formation provides an alternative copper-secretion mechanism in Gram-negative bacteria (Lima et al. 2022).

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