The NIH Common Fund Extracellular RNA Communication program (https://commonfund.nih.gov/exrna) was established in 2012 to uncover fundamental principles of exRNA biogenesis and function. ExRNAs are transported in body fluids in association with an array of carrier vehicles of varying complexity including extracellular vesicles (EVs), ribonucleoproteins (RNPs), and lipoproteins (LPPs). The respective contributions of EVs, RBPs, and LPPs to exRNA biodistribution and function is not clear.
Determining which exRNAs are transported by each specific carrier vehicle (EV, RNP, or LPP) is essential for elucidating exRNA sorting pathways and identifying associated cargo that may confer targeting or functionality. Currently available separation technologies are time-consuming and do not adequately discriminate exRNAs encapsulated in EVs from exRNAs associated with non-vesicular RNPs or LPPs. Further, current technologies do not permit single EV isolation and analysis thereby limiting our understanding of EV heterogeneity and ability to sort and identify EVs from complex biofluids by their cell or origin.
These technology challenges will be addressed in the second stage of the NIH Common Fund exRNA Communication Program. Development of novel tools, technologies, and resources will complement Stage 1, fill remaining knowledge and technology gaps, and facilitate the generation of community accepted standards. Meeting the goals of the Stage 2 Initiatives will have a transformative effect on the field of exRNA biology and will enable a greater understanding of the fundamental role of exRNAs in intercellular signaling and the translational potential to diagnose and treat diseases.