Extracellular Vesicles and the Promise of Continuous Liquid Biopsies

Abstract

The rapid and accurate diagnosis of patients with minimally invasive procedures was once only found in science fiction. However, the discovery of extracellular vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of inexpensive next generation sequencing techniques and EV purification protocols, promises to make science fiction a reality. Purifying and sequencing the RNA content of EV from routine blood draws and urine samples are likely to enable pathologists and physicians to diagnose and track the progress of diseases in many inaccessible tissues in the near future. Here we present the evolutionary background of EV, summarize the biology of EV formation and cargo selection, and discuss the current barriers to making continuous liquid biopsies through the use of EV a science reality.

Keywords: Cell-free RNA; Exosomes; Extracellular vesicles; Liquid biopsy; Microvesicles.

Fig. 1.

Extracellular vesicles are found in all domains of life, including Archaea [1,2], Bacteria [3-5], and Eukaryotes [3-15].

Fig. 2.

Production of exosomes and microvesicles in cells. Microvesicles are generated from the budding of the plasma membrane (A). Exosomes are generated from the inward budding of multi-vesicular endosomes (MVEs) by the action of multiple proteins (B) and result in the release of exosomes (C) if the MVE is targeted to the plasma membrane instead of the late endosome.