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Press release
Thursday, April 4, 2019
Cells use RNA to communicate; researchers may be able to translate this information into clinical applications.
Ribonucleic acid (RNA), a biomolecule, is essential for cell function. RNA plays a variety of roles in determining how the information in our genes determines how cells behave. One of its roles is to carry the information encoded by our genes from the nucleus of the cell to the rest of the cell, where other components of the cell can act. Through a program supported by the National Institutes of Health, researchers have now defined how RNA also participates in the transmission of information outside of cells, called extracellular RNA or exRNA. This new role of RNA in cell-to-cell communication has led to new discoveries of disease biomarkers and potential therapeutic targets.
The extracellular RNA communication program supported by the NIH Joint Fund was launched in 2013 to revitalize progress in this new area of biomedical research. Scientists from the Extracellular RNA Communication Consortium (ERCC) have published their findings in more than 480 articles, including a historical collection of articles on the biology and possible clinical applications of exRNA in the Cell family of journals.
"Cells using RNA to talk to each other constitute a significant shift in our understanding of RNA biology," said NIH Director Francis S. Collins, MD, Ph.D. Domain was ripe for an NIH investment to stimulate early discoveries and create resources that the entire research community could use to explore this new role of the NRA. "
ERCC researchers have explored the basic biology of exARNs, including the making of exARN molecules and their transport packaging (or transporters), their expulsion by producer cells and their uptake by target cells, and what the exARN molecules did when they arrived at their destination. They have encountered surprising complexity both in the types of transporters that carry exARN molecules between cells and in the different types of exRNA molecules associated with transporters. The researchers had to demonstrate exceptional creativity in the development of molecular and data-centric tools to begin to understand the complexity. They found that the type of media affected how exARN messages were sent and received.
As newsletters between cells, exARN molecules and their transporters allow researchers to intercept exARN messages to determine if they are associated with a disease. If scientists could modify or design exARN messages for designers, this could be a new way to treat diseases. ERCC researchers have identified potential exARN biomarkers for nearly 30 diseases, including cardiovascular diseases, brain and central nervous system diseases, pregnancy complications, glaucoma, diabetes, autoimmune diseases -immune and multiple types of cancer.
For example, researchers found that exRNAs in urine were a promising biomarker for muscular dystrophy, with current studies using markers obtained from painful muscle biopsies. Other researchers at ERCC have laid the foundation for the use of exARN RNA as therapeutic agents. Preliminary studies showed how researchers could load exARN molecules into appropriate carriers and target carriers for the desired receptor cells, and also determined whether modified transporters could have adverse effects. In a preclinical study, scientists designed carriers with designer-based RNA messages to target laboratory-grown breast cancer cells displaying some protein on their surface. In an animal model of breast cancer with cell surface protein, the researchers found a reduction in tumor growth after modified carriers deposited their cargo of RNA.
The ERCC also aimed to create a catalog of ex-RNA molecules found in human biofluids such as plasma, saliva and urine. Program researchers analyzed more than 50,000 samples from more than 2,000 donors, generating exRNA profiles of 13 biofluids. This included over 1000 exARN profiles of healthy volunteers. ERCC researchers have discovered that ex-RNA profiles vary widely among healthy individuals depending on characteristics such as age and environmental factors such as exercise. This means that ex-RNA profiles can provide important and detailed information on health and disease, but careful comparisons with ex-RNA data generated from people with similar characteristics should be made.
These profiles are accessible to the public via the exARN portal, created as part of the ERCC's goal of developing and sharing exARN data, technologies and IT tools. The exARN portal is a central point of access for exARN resources, including protocols, data, reagents, software, and data standards. These resources are at the disposal of the research community to advance the new field of ex-RNA biology more rapidly.
In the summer of 2019, the exARN communication program will enter a second step to tackle the complexity of exARN molecules and the diversity of media. ERCC Stage 2 researchers will develop tools to effectively and reproducibly isolate, identify and analyze the different types of carriers and their ex-RNA cargoes, and to analyze a carrier and his load at a time. These tools will be shared with the research community to fill gaps in knowledge generated during the first phase of the program and to continue to advance this area.
The ExRNA Communication program is funded by the NIH Common Fund. It is managed by a trans-NIH working group and led by the staff of the Common Fund. National Center for the Advancement of Translational Sciences; National Cancer Institute; National Institute of the Heart, Lungs and Blood; and National Institute for Combating Drug Abuse.
This press release describes basic research. Basic research increases our understanding of human behavior and biology, which is fundamental to advancing new and improved methods of disease prevention, diagnosis and treatment. Science is an unpredictable and progressive process – every breakthrough in research builds on past discoveries, often unexpectedly. Most clinical progress would not be possible without the knowledge of basic fundamental research.
About the NIH common fund: The NIH common fund encourages collaboration and supports a series of trans-NIH programs with exceptional impact. The Common Fund programs are managed by the Office of Strategic Coordination of the Program Coordination, Planning and Strategic Initiatives Division of the NIH Director's Office, in partnership with NIH institutes, centers and offices. Further information is available on the Common Fund website: https://commonfund.nih.gov.
About the National Institutes of Health (NIH):
The NIH, the country's medical research agency, has 27 institutes and centers and is part of the US Department of Health and Human Services. NIH is the lead federal agency that conducts and supports basic, clinical and translational medical research. She studies causes, treatments and treatments for common and rare diseases. For more information on NIH and its programs, visit www.nih.gov.
NIH … transforming discovery into health®
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