Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop
Kang Li, … , Robert L. Raffai, T. Kevin Howcroft
Kang Li, … , Robert L. Raffai, T. Kevin Howcroft
Published April 5, 2018
Citation Information: JCI Insight. 2018;3(7):e98942. https://doi.org/10.1172/jci.insight.98942.
View: Text | PDF
Review

Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop

  • Text
  • PDF
Abstract

Extracellular RNA (exRNA) has emerged as an important transducer of intercellular communication. Advancing exRNA research promises to revolutionize biology and transform clinical practice. Recent efforts have led to cutting-edge research and expanded knowledge of this new paradigm in cell-to-cell crosstalk; however, gaps in our understanding of EV heterogeneity and exRNA diversity pose significant challenges for continued development of exRNA diagnostics and therapeutics. To unravel this complexity, the NIH convened expert teams to discuss the current state of the science, define the significant bottlenecks, and brainstorm potential solutions across the entire exRNA research field. The NIH Strategic Workshop on Extracellular RNA Transport helped identify mechanistic and clinical research opportunities for exRNA biology and provided recommendations on high priority areas of research that will advance the exRNA field.

Authors

Kang Li, Rodosthenis S. Rodosthenous, Fatah Kashanchi, Thomas Gingeras, Stephen J. Gould, Lillian S. Kuo, Peter Kurre, Hakho Lee, Joshua N. Leonard, Huiping Liu, Tania B. Lombo, Stefan Momma, John P. Nolan, Margaret J. Ochocinska, D. Michiel Pegtel, Yoel Sadovsky, Francisco Sánchez-Madrid, Kayla M. Valdes, Kasey C. Vickers, Alissa M. Weaver, Kenneth W. Witwer, Yong Zeng, Saumya Das, Robert L. Raffai, T. Kevin Howcroft

×

Figure 1

Outstanding questions and research opportunities in extracellular RNA biology.

Options: View larger image (or click on image) Download as PowerPoint
Outstanding questions and research opportunities in extracellular RNA bi...
Advancing research on extracellular RNA (exRNA) communication holds great potential for transforming translational science. The NIH Strategic Workshop on Extracellular RNA Transport identified many unanswered fundamental questions and unmet technical challenges and generated recommendations on high priority areas that could catalyze research across the exRNA field. (1) RNA sorting and loading. What are the RNA structural features and RNA-binding proteins (RBPs) that guide RNA to different extracellular vesicle (EV) subtypes, i.e., exosomes and microvesicles? (2) EV biogenesis and heterogeneity. What are the molecules and molecular machineries specific to individual EV biogenesis pathways, i.e., (a) direct membrane budding of microvesicles; (b) endosomal sorting complexes required for transport–dependent (ESCRT-dependent) or (c) ceramide-dependent multivesicular body (MVB) formation? How do different biogenesis pathways contribute to EV heterogeneity? (3) EV secretion. What are the molecular determinants that direct the secretion of EV subtypes along different export pathways? (4) EV isolation. What are the unique biophysical/biochemical characteristics of each EV subtype that could be used for functionally separating EV subtypes from each other and from other exRNA carriers, i.e., RBP, lipoprotein (LPP)? (5) EV uptake. What are molecular interactions between EVs and recipient cells that determine targeted delivery of exRNAs? (6) exRNA functional fate in recipient cells. How are exRNAs processed and through what forms do exRNAs execute their effector functions in recipient cells? (7) exRNA tracking and functional effect in vivo. What are the model systems that allow targeted modification and disruption of EVs to enable monitoring exRNA dynamics in vivo and unambiguous demonstration of their physiological relevance? Illustrated by Rachel Davidowitz.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts