Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

SIMPLE SUMMARY: We reviewed characterization and the role of DNAs derived from extracellular vesicles focusing on its use for identifying biomarkers. Extracellular vesicles contain double-stranded genomic DNA reflecting the mutational status and methylation profile of the parental tumor cells. Many studies demonstrated higher stability, sensitivity, and specificity of extracellular vesicle DNAs in comparison to cell-free DNAs, demonstrating a high potential for clinical application as a source for liquid biopsy. Moreover, the horizontally transfer ability of extracellular vesicle DNAs could be utilized in therapeutics. ABSTRACT: Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors. The existence of DNA and its stability make EVs a useful source of biomarkers. However, fundamental research on EV DNA remains limited, and many aspects of EV DNA are poorly understood. This review examines the known characteristics of EV DNA, biogenesis of DNA-containing EVs, methylation, and next-generation sequencing (NGS) analysis using EV DNA for biomarker detection. On the basis of this knowledge, this review explores how EV DNA can be incorporated into diagnosis and prognosis in clinical settings, as well as gene transfer of EV DNA and its therapeutic potential.