Bioactive DNA from extracellular vesicles and particles

Extracellular vesicles (EVs) and particles (EPs) have recently emerged as active carriers of molecular biomarkers and mediators of intercellular communication. While most investigations have focused exclusively on the protein, lipid and RNA constituents of these extracellular entities, EV/EP DNA remains poorly understood, despite DNA being found in association with virtually all EV/EP populations. The functional potential of EV/EP DNA has been proposed in a number of pathological states, including malignancies and autoimmune diseases. Moreover, the effectiveness of cell-free DNA as the biomarker of choice in emerging liquid biopsy applications highlights the role that EV/EP DNA may play as a novel disease biomarker.

Researchers from the University of Toronto provide a comprehensive overview of EV/EP DNA studies conducted to date, with a particular focus on the roles of EV/EP DNA as a functional mediator and molecular biomarker in various pathologic states. They also discuss what is currently known about the origins, structure, localisation and distribution of EV/EP DNA, highlighting current controversies as well as opportunities for future investigation.

EV/EP DNA directly influences physiological function by acting on recipient cells

Fig. 3

EV/EPs deliver DNA to the recipient cell cytosol. a Horizontal gene transfer. EV/EP DNA can translocate to the recipient cell nucleus or mitochondria, where it is integrated into the host genome. Subsequent transcription of this DNA heavily influences recipient cell function, and phenotypic changes depend on the genotype of cells from which the EV/EP DNA was derived. b Activation of oncogenic pathways. EV/EP DNA can activate or cause the up-regulation of various intracellular signalling proteins, such as STAT3, causing translocation to the nucleus and over-expression of oncogenes that drive a pro-tumourigenic phenotype in the recipient cell. c Activation of inflammatory pathways. EV/EP DNA can trigger various cytosolic DNA receptors, including AIM2 (which subsequently produces interleukins) and cGAS. Activation of cGAS causes downstream release of Type I Interferons that induce inflammatory responses unique to the disease context.

Malkin EZ, Bratman SV. (2020) Bioactive DNA from extracellular vesicles and particles. Cell Death Dis 11, 584. [article]

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