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Molecules 2017, 22(1), 139; doi:10.3390/molecules22010139

Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases

1
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 117600, Singapore
2
Immunology Program, Life Science Institute, National University of Singapore, Singapore 117456, Singapore
3
CREATE Program, National University of Singapore, Singapore 138602, Singapore
*
Author to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 2 November 2016 / Revised: 5 January 2017 / Accepted: 8 January 2017 / Published: 17 January 2017
(This article belongs to the Special Issue Nucleic Acid-based Drug)
View Full-Text   |   Download PDF [1657 KB, uploaded 17 January 2017]   |  

Abstract

Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology. Corticosteroids have been widely prescribed for the treatment of asthma, COPD, and IPF. However, the effectiveness of corticosteroids as an anti-inflammatory drug is limited by steroid resistance in severe asthma, the majority of COPD cases, and pulmonary fibrosis. There is an urgent medical need to develop target-specific drugs for the treatment of these respiratory conditions. Oligonucleotide therapies, including antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) are now being evaluated both pre-clinically and clinically as potential therapeutics. The mechanisms of action of ASO and siRNA are highly target mRNA specific, ultimately leading to target protein knockdown. miRNA has both biomarker and therapeutic values, and its knockdown by a miRNA antagonist (antagomir) has a broader but potentially more non-specific biological outcome. This review will compile the current findings of oligonucleotide therapeutic targets, verified in various respiratory disease models and in clinical trials, and evaluate different chemical modification approaches to improve the stability and potency of oligonucleotides for the treatment of respiratory diseases. View Full-Text
Keywords: asthma; COPD; pulmonary fibrosis; antisense oligonucleotide; small-interfering RNA; microRNA asthma; COPD; pulmonary fibrosis; antisense oligonucleotide; small-interfering RNA; microRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Liao, W.; Dong, J.; Peh, H.Y.; Tan, L.H.; Lim, K.S.; Li, L.; Wong, W.-S.F. Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases. Molecules 2017, 22, 139.

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