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MicroRNA Targets for Asthma Therapy

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Lung Inflammation in Health and Disease, Volume I

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1303))

Abstract

Asthma is a chronic inflammatory obstructive lung disease that is stratified into endotypes. Th2 high asthma is due to an imbalance of Th1/Th2 signaling leading to abnormally high levels of Th2 cytokines, IL-4, IL-5, and IL-13 and in some cases a reduction in type I interferons. Some asthmatics express Th2 low, Th1/Th17 high phenotypes with or without eosinophilia. Most asthmatics with Th2 high phenotype respond to beta-adrenergic agonists, muscarinic antagonists, and inhaled corticosteroids. However, 5–10% of asthmatics are not well controlled by these therapies despite significant advances in lung immunology and the pathogenesis of severe asthma. This problem is being addressed by developing novel classes of anti-inflammatory agents. Numerous studies have established efficacy of targeting pro-inflammatory microRNAs in mouse models of mild/moderate and severe asthma. Current approaches employ microRNA mimics and antagonists designed for use in vivo. Chemically modified oligonucleotides have enhanced stability in blood, increased cell permeability, and optimized target specificity. Delivery to lung tissue limits clinical applications, but it is a tractable problem. Future studies need to define the most effective microRNA targets and effective delivery systems. Successful oligonucleotide drug candidates must have adequate lung cell uptake, high target specificity, and efficacy with tolerable off-target effects.

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Abbreviations

AHR :

airway hyperreactivity

APC:

antigen presenting cell

ASM :

airway smooth muscle

BALF :

bronchoalveolar lavage fluid

CDG :

cyclic diguanosine monophosphate, bis-(3′-5′)-cyclic dimeric GMP

HDM :

house dust mite

IFN :

interferon

IL :

interleukin

LNA :

locked nucleic acid

mAb:

monoclonal antibody

miR :

microRNA

mRNA:

messenger RNA

OVA:

ovalbumin

RISC :

RNA-induced silencing complex

Th1 :

type 1 helper

Th17 :

type 17 helper

Th2 :

type 2 helper

Th2high :

type 2 high

Th2low :

type 2 low

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Acknowledgments

Preparation of this manuscript was supported by a grant to WTG from the National Institute of Allergy and Infectious Diseases (AI116985).

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  1. Critical Care Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Sabrina C. Ramelli

  2. Department of Pharmacology, Reno School of Medicine, University of Nevada, Reno, NV, USA

    William T. Gerthoffer

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  1. Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA

    Yong-Xiao Wang

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Ramelli, S.C., Gerthoffer, W.T. (2021). MicroRNA Targets for Asthma Therapy. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume I. Advances in Experimental Medicine and Biology, vol 1303. Springer, Cham. https://doi.org/10.1007/978-3-030-63046-1_6

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