Extracellular RNA Communication

Once thought to exist only within cells, in a paradigm shift for science, RNA is now known to be exported from cells as “extracellular RNA (exRNA)” and to play a role in mechanisms of cell-to-cell communication. The Extracellular RNA Communication (ERC) program is working to understand exRNA biology and accelerate development of exRNAs as potential therapeutics and diagnostics. 

The first stage of the program established data standards, a data portal, and developed novel tools and reagents. The program also cataloged exRNA molecules found in human biofluids like plasma, saliva, and urine from over 2000 donors. Researchers also identified potential exRNA biomarkers for nearly 30 diseases, including cardiovascular disease, pregnancy complications, glaucoma, diabetes, and multiple types of cancer.

The exRNA program was approved for continuation in 2019 and focuses tool and technology development to address major roadblocks to understanding exRNAs, including better understanding of the larger complexes like Extracellular Vesicles (EVs) that carry exRNA through the body. 

A lack of uniform methods to purify and characterize EVs and the molecules they carry, like RNA, remain challenging scientific hurdles. Better understanding of the heterogeneity of EV subpopulations and of non-EV RNA-carrying structures are needed to understand which and how these carries send those RNA messages to other cells. Specifically, the exRNA program’s second stage will develop methods to rapidly sort complex biofluids into different populations, as well as develop techniques to sort and isolate different types of EV carriers. Program researchers will characterize the exRNA found in those EV subpopulations based on cell of origin and intended target cell. The goal is enabling a greater understanding of the fundamental role of exRNAs in intercellular signaling and the translational potential to diagnose and treat diseases.