Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS

Author:

Vaswani Chirag M.12ORCID,Simone Julia3,Pavelick Jacqueline L.4,Wu Xiao2,Tan Greaton W.12ORCID,Ektesabi Amin M.24ORCID,Gupta Sahil5,Tsoporis James N.2,dos Santos Claudia C.12467ORCID

Affiliation:

1. Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada

2. Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada

3. Department of Medicine, McMaster University, Hamilton, ON L8V 5C2, Canada

4. Institute of Medical Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada

5. Faculty of Medicine, School of Medicine, The University of Queensland, Herston, QLD 4006, Australia

6. Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada

7. Interdepartmental Division of Critical Care, St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada

Abstract

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and increased membrane permeability, which represents the leading cause of mortality in ICUs. Mechanical ventilation strategies are at the forefront of supportive approaches for ARDS. Recently, an increasing understanding of RNA biology, function, and regulation, as well as the success of RNA vaccines, has spurred enthusiasm for the emergence of novel RNA-based therapeutics. The most common types of RNA seen in development are silencing (si)RNAs, antisense oligonucleotide therapy (ASO), and messenger (m)RNAs that collectively account for 80% of the RNA therapeutics pipeline. These three RNA platforms are the most mature, with approved products and demonstrated commercial success. Most recently, miRNAs have emerged as pivotal regulators of gene expression. Their dysregulation in various clinical conditions offers insights into ARDS pathogenesis and offers the innovative possibility of using microRNAs as targeted therapy. This review synthesizes the current state of the literature to contextualize the therapeutic potential of miRNA modulation. It considers the potential for miR-based therapeutics as a nuanced approach that incorporates the complexity of ARDS pathophysiology and the multifaceted nature of miRNA interactions.

Funder

Canadian Institutes of Health Research

Publisher

MDPI AG

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