Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Pharmaceutical Sciences, University at Buffalo, USA.
³ Department of Physics, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
⁴ Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
⁵ Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599, USA.
⁶ UNC Neuroscience Microscopy Core, Carolina Institute for Developmental Disabilities, UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 25799, USA.
⁷ UNC Neuroscience Microscopy Core, Carolina Institute for Developmental Disabilities, UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 25799, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, NC 27599, USA.
⁸ Department of Systems and Information Engineering, University of Virginia, Charlottesville, 22903, USA.
⁹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: julianen@email.unc.edu.

PMID: 39111600
PMCID: PMC11550487 (available on 2025-10-01)
DOI: 10.1016/j.jconrel.2024.07.043

Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles

Emily E Bonacquisti et al. J Control Release. 2024 Oct.

. 2024 Oct:374:349-368.

doi: 10.1016/j.jconrel.2024.07.043. Epub 2024 Aug 22.

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Pharmaceutical Sciences, University at Buffalo, USA.
³ Department of Physics, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
⁴ Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
⁵ Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599, USA.
⁶ UNC Neuroscience Microscopy Core, Carolina Institute for Developmental Disabilities, UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 25799, USA.
⁷ UNC Neuroscience Microscopy Core, Carolina Institute for Developmental Disabilities, UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 25799, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, NC 27599, USA.
⁸ Department of Systems and Information Engineering, University of Virginia, Charlottesville, 22903, USA.
⁹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: julianen@email.unc.edu.

PMID: 39111600
PMCID: PMC11550487 (available on 2025-10-01)
DOI: 10.1016/j.jconrel.2024.07.043

Abstract

Extracellular vesicles (EVs), or exosomes, play important roles in physiological and pathological cellular communication and have gained substantial traction as biological drug carriers. EVs contain both short and long non-coding RNAs that regulate gene expression and epigenetic processes. To fully capitalize on the potential of EVs as drug carriers, it is important to study and understand the intricacies of EV function and EV RNA-based communication. Here we developed a genetically encodable RNA-based biomaterial, termed EXO-Probe, for tracking EV RNAs. The EXO-Probe comprises an EV-loading RNA sequence (EXO-Code), fused to a fluorogenic RNA Mango aptamer for RNA imaging. This fusion construct allowed the visualization and tracking of EV RNA and colocalization with markers of multivesicular bodies; imaging RNA within EVs, and non-destructive quantification of EVs. Overall, the new RNA-based biomaterial provides a useful and versatile means to interrogate the role of EVs in cellular communication via RNA trafficking to EVs and to study cellular sorting decisions. The system will also help lay the foundation to further improve the therapeutic efficacy of EVs as drug carriers.

Keywords: Biomaterials; Extracellular vesicles; RNA; Trafficking.

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Conflict of interest statement

Declaration of competing interest JN, SF, and EB are inventors on the patent applications of the EXO-Code technology evaluated in this paper that have been licensed to Exopharm and have received royalties. These relationships have been disclosed to and are under management by UNC-Chapel Hill.

References

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Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles

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Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles

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