In the past decade, extracellular vesicles (EVs) have emerged as key players in homeostasis as well as in the pathogenesis of diseases owing to the variety of the cargos they can carry and their robust interactions between EVs and target cells. Accordingly, the development of an exosome/EV-based liquid biopsy for early detection and for monitoring the progression of diseases heralds a new era for precision medicine. However, the advance of the EV research is impeded by our inability to study these membrane-bound messengers at the single EV level. Indeed, for example, little is known as to how many protein molecules an EV of a given size can display on its surface. There is a paucity on the differences in terms of the nature and the number of the RNA/DNA/protein cargos between each individual EV. Thus, one of the biggest challenges in the EV field is the molecular nature and its biochemical and cell biological mechanisms underlying EV heterogeneity. To undertake the challenge, we need new tools.
Nucleic acid aptamers, also known as chemical antibodies, are 20-25-fold smaller than a monoclonal antibody. Due to its exquisite specificity, smaller size and tunable kD/on-rate/off-rate, aptamers emerge not only as a promising therapeutics and/or diagnostic tool for translational EV research but also a novel avenue for addressing EV heterogeneity at the single EV level. Here, we will present the latest advances in terms of the findings and strategies on how aptamers can potentially transform EV research. In particular, the advantages of using aptamers over antibodies in EV research will be elaborated with solid data as well as theoretical considerations.