The NIH Extracellular RNACommunication Program's initiative on clinical utility of extracellular RNAs and therapeutic agents and developing scalable technologies is reviewed here. Background information and details of the projects are presented. The work has focused on modulation of target cell fate by extracellular vesicles (EVs) and RNA. Work on plant-derived vesicles is of intense interest, and non-mammalian sources of vesicles may represent a very promising source for different therapeutic approaches. Retro-viral-like particles are intriguing. Clearly, EVs share pathways with the assembly machinery of several other viruses, including human endogenous retrovirals (HERVs), and this convergence may explain the observation of viral-like particles containing viral proteins and nucleic acid in EVs. Dramatic effect on regeneration of damaged bone marrow, renal, pulmonary and cardiovascular tissue is demonstrated and discussed. These studies show restoration of injured cell function and the importance of heterogeneity of different vesicle populations. The potential for neural regeneration is explored, and the capacity to promote and reverse neoplasia by EVexposure is described. The tremendous clinical potential of EVs underlies many of these projects, and the importance of regulatory issues and the necessity of general manufacturing production (GMP) studies for eventual clinical trials are emphasized. Clinical trials are already being pursued and should expand dramatically in the near future.
Bibliographical noteFunding Information:
Xandra O. Breakefield, general, financial and material support U19 CA179563 supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director. 1UH2TR000880 (Peter Quesenberry, MD) Agency: NIH/NIDDK. We are grateful to the James Graham Brown Cancer Center, University of Louisville. Our special thanks extends to Dr. Donald M Miller (Principal Investigator and Director of the Cancer Center) and Dr. Rebecca Redman (Co-Principal Investigator) from the James Graham Brown Cancer Center for both clinical trials. This work was supported by grants from the National Institutes of Health (NIH) (UH2TR000875) and the Louisville Veterans Administration Medical Center (VAMC) Merit Review Grants (H.-G.Z.). Vanderbilt University, Nashville, TN: R01 CA163563, U19 CA179514, P50 CA095103 (SPORE). NIH-NCATS (1UH2 TR000928-02). Department of Urology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112.
- Cell fate change
- Extracellular vesicles
- Functional effects
- Pulmonary heart disease