Unraveling extracellular vesicle DNA: Biogenesis, functions, and clinical implications

Extracellular Vesicles (EVs) have emerged as essential carriers of molecular biomarkers and mediators of intercellular communication. While previous studies have predominantly focused on EV proteins, lipids, and RNA, the role of EV-derived DNA (EV-DNA) remains relatively unexplored. Understanding EV-DNA is crucial, given its association with nearly all EV populations. This review aims to comprehensively summarize existing EV-DNA research, emphasizing its functional significance and potential as a disease biomarker. By bridging the gap in our understanding, we shed light on the origins, structure, localization, and distribution of EV-DNA. We analyze a wide range of studies, investigating EV-DNA across various pathological conditions. Our review encompasses experimental methods, theoretical approaches, and clinical observations, providing a holistic view of EV-DNA research. We discuss the biogenesis mechanisms of different EV subtypes, the available isolation methods for these subtypes, and consider their origins and variability under different conditions. EV-DNA exhibits remarkable stability and reflects genomic alterations, making it a promising candidate for liquid biopsy applications. From cancer diagnostics to treatment monitoring, EV-DNA holds significant potential. The findings underscore the importance of EV-DNA as an innovative biomarker. As research continues, EV-DNA may revolutionize disease detection, prognosis, and therapeutic strategies.