Extracellular vesicle-derived DNA methylation cargos: linking disease mechanisms, biomarkers, and therapeutic potential – a mini review

Extracellular vesicles (EVs) are lipid-bilayered nanoparticles that are released by all cells and carry cargos reflective of their cell of origin, including nucleic acids, proteins, and lipids. This narrative review provides a brief overview of EVs and their characterization and then examines the current literature on EV-associated DNA cargos and the assays used to investigate methylation patterns in both EV-DNA and the DNA of EV-targeted cells. It further explores how EV cargos, including DNA methylation-related enzymes and miRNAs, may influence the epigenetic landscape of target cells. We also summarize current evidence on the utility of methylated EV-DNA as a biomarker and examine the therapeutic potential of EVs engineered to deliver DNA-modifying molecules in diseases driven by aberrant DNA methylation. Both key fields of EV research are rapidly gaining momentum. Integrating these insights is essential for advancing our understanding of disease mechanisms and developing mechanistically informed biomarkers for early diagnosis and personalized treatment across a range of conditions, from cancer and neurological disease to fetal pathologies.