Extracellular RNA communication: A decade of NIH common fund support illuminates exRNA biology

The discovery that extracellular RNAs (exRNA) can act as endocrine signalling molecules established a novel paradigm in intercellular communication. ExRNAs can be transported, both locally and systemically in virtually all body fluids. In association with an array of carrier vehicles of varying complexity, exRNA can alter target cell phenotype. This highlights the important role secreted exRNAs have in regulating human health and disease. The NIH Common Fund exRNA Communication program was established in 2012 to accelerate and catalyze progress in the exRNA biology field. The program addressed both exRNA and exRNA carriers, and served to generate foundational knowledge for the field from basic exRNA biology to future potential clinical applications as biomarkers and therapeutics. To address scientific challenges, the exRNA Communication program developed novel tools and technologies to isolate exRNA carriers and analyze their cargo. Here, we discuss the outcomes of the NIH Common Fund exRNA Communication program, as well as the evolution of exRNA as a scientific field through the analysis of scientific publications and NIH funding. ExRNA and associated carriers have potential clinical use as biomarkers, diagnostics, and therapeutics. Recent translational applications include exRNA-related technologies repurposed as novel diagnostics in response to the COVID-19 pandemic, the clinical use of extracellular vesicle-based biomarker assays, and exRNA carriers as drug delivery platforms. This comprehensive landscape analysis illustrates how discoveries and innovations in exRNA biology are being translated both into the commercial market and the clinic. Analysis of program outcomes and NIH funding trends demonstrate the impact of this NIH Common Fund program.