# Investigating the transfer of miRNAs by exosomes during inflammation

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $451,952

## Abstract

Abstract
 Mammalian microRNAs are critical regulators of several human diseases. As a result, therapeutic
manipulation of miRNAs in diseased tissues has emerged as a promising approach to combating human
disorders, and has had success in some settings. Yet, effective delivery of miRNAs or their inhibitors to many
cell and tissue types continues to be a major challenge, and this underscores the need for improved methods
of small RNA delivery to relevant cell types. Recent reports have demonstrated that miRNAs can be released
from cells in small lipid vesicles called exosomes. In turn, the exosomes can deliver miRNAs to recipient cells,
and this system is thought to constitute a novel form of intercellular communication. This process includes an
endogenous miRNA delivery mechanism that is largely uncharacterized, yet could provide valuable insights
into how therapeutic miRNA delivery can be improved and how inflammatory responses are regulated. Our
preliminary data demonstrate that mouse bone marrow derived dendritic cells (BMDCs) produce exosomes
that contain specific miRNAs, including the inflammatory regulators miR-155 and mIR-146a, that can be
delivered to recipient immune cells and subsequently mediate target knockdown both in vitro and in vivo. This
results in an altered response to endotoxin both in vitro and in vivo, which provides experimental evidence that
exosome-transferred miRNAs provide a novel layer of regulating inflammation. Further, we have also been
able to successfully load specific miRNA mimics into exosomes and demonstrate that they can be delivered to
recipient cells in a functionally relevant manner. As a result of these findings, we hypothesize that exosomal
miRNAs play novel regulatory roles during physiologically relevant inflammatory responses, and that through
an improved understanding of this process, exosomes can ultimately be coopted to deliver specific miRNA
cocktails in a therapeutically relevant manner. We will carry out the following specific aims to test these
predictions. First, we will define the process of exosomal miRNA delivery to immune cells. Next, we will
determine the functional relevance of exosomal miRNAs during inflammation using radiation chimeras and
Rab27a/b DKO mice with impaired exosome production. Finally, we will engineer custom exosomes and test
their impact on inflammatory disease. Together, this project will shed light on how exosome transfer of miRNAs
is regulated, determine the role of this system during physiologically relevant inflammation, and begin to
understand the translational potential of this novel process.

## Key facts

- **NIH application ID:** 9891940
- **Project number:** 5R01AI123106-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Ryan M O'Connell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,952
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891940

## Citation

> US National Institutes of Health, RePORTER application 9891940, Investigating the transfer of miRNAs by exosomes during inflammation (5R01AI123106-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9891940. Licensed CC0.

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