Clinical applications of extracellular vesicle long RNAs

Extracellular vesicles (EVs), primarily exosomes and microvesicles, are critical intercellular mediators of communication. Over the past decade, improved knowledge and methodologies have enabled the detection and quantification of RNA species in EVs, despite their extremely low levels. Recently, EV-associated long RNAs (exLRs) have been drawing much attention. Delivered by EVs, they have higher stability, greater difference in temporal and spatial expression, and the capacity to remodel both proximal and distal recipient cells. These properties guarantee their roles as biomarkers, therapeutic targets, vaccines, and gene therapy agents in a wide range of human diseases. Despite the progress in this area of research, limitations in both knowledge and methodologies have hindered its further development. Herein, we comprehensively reviewed studies related to exLRs, including protein-coding messenger RNAs (mRNAs) and noncoding RNAs (long noncoding RNAs and circular RNAs) in EVs to indicate their value in the diagnosis and treatment of human diseases; we also present a series of yet unsettled issues in this novel area, hence providing insights for future studies.