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Extracellular vesicle-associated nucleic acids (EV-NAs) refer to the diverse repertoire of RNA and DNA molecules, including messenger RNA (mRNA), microRNA (miRNA), and double-stranded DNA, that are sequestered within or associated with the surface of extracellular vesicles (EVs) (Valadi et al., 2007, Nature Cell Biology). These nucleic acids are protected from degradation by the EV lipid bilayer and serve as essential mediators of horizontal gene transfer and intercellular communication, influencing biological processes such as immune response and tissue repair (Kalluri & LeBleu, 2020, Science). In the context of disease, EV-NAs are pivotal in the progression of cancer, neurodegeneration, and cardiovascular disorders by modulating the microenvironment and promoting pathological signaling (Thakur et al., 2014, Cancer Discovery). Although EV-NAs are not traditional single-protein drug targets, they are highly valued as non-invasive biomarkers for liquid biopsies and are being harnessed as delivery vehicles for therapeutic RNA-based drugs (Wiklander et al., 2019, Science Translational Medicine). Pharmacological intervention typically involves the use of small molecules like GW4869 to inhibit EV secretion, thereby reducing the systemic spread of pathogenic nucleic acid cargo (Essandoh et al., 2015, Journal of Biological Chemistry). Furthermore, the engineering of EVs to carry specific siRNA or mRNA payloads represents a burgeoning field in precision medicine, aiming to target previously undruggable pathways.
Inhibition of extracellular vesicle biogenesis and secretion, or therapeutic delivery of functional nucleic acids via engineered vesicles.
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