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Review
. 2021 Jul 29;13(15):3827.
doi: 10.3390/cancers13153827.

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Jae Young Hur  1   2 , Kye Young Lee  1   3
Affiliations
Review

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Jae Young Hur et al. Cancers (Basel). .

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.

Keywords: EV DNA; exosome; extracellular vesicle; gene transfer; liquid biopsy; methylation; microvesicle; next-generation sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Characterization of DNA-loaded EVs. (A) DNA can be enclosed within EVs, (B) attached to the outer surface of EV, or (C) enclosed and attached to the outer surface. EV—extracellular vesicle.
Figure 2
Figure 2
Detection of dsDNA in BALF EVs using immuno-EM. (A) Single vesicle and (B) multilayer vesicle. The solid black dots indicate DNA (indicated by red arrows). dsDNA—double-stranded DNA; BALF—bronchoalveolar lavage fluid; EV—extracellular vesicle; EM—electron microscopy.
Figure 3
Figure 3
Body fluids as a source of DNA derived from EV. EV—extracellular vesicle; BALF—bronchoalveolar lavage fluid.
Figure 4
Figure 4
DNA loading into EVs via various mechanisms. DNA can be loaded into EVs through a CD63-mediated DNA shuttle or emerin-mediated nucleus instability and shedding. Other possible unknown mechanisms could include the loading of cytosolic DNA that originated from the nucleus and mitochondria by oxidative stress. EV—extracellular vesicle.
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