Royal College of Surgeons in Ireland
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Alpha-1 antitrypsin-a target for microRNA-based therapeutic development for cystic fibrosis

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journal contribution
posted on 2022-10-18, 16:30 authored by Alison M D Hunt, Arlene MA Glasgow, Hilary HumphreysHilary Humphreys, Catherine GreeneCatherine Greene

Cystic fibrosis (CF) is an autosomal recessive genetic disorder arising from mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Disruption to normal ion homeostasis in the airway results in impaired mucociliary clearance, leaving the lung more vulnerable to recurrent and chronic bacterial infections. The CF lung endures an excess of neutrophilic inflammation, and whilst neutrophil serine proteases are a crucial part of the innate host defence to infection, a surplus of neutrophil elastase (NE) is understood to create a net destructive effect. Alpha-1 antitrypsin (A1AT) is a key antiprotease in the control of NE protease activity but is ineffective in the CF lung due to the huge imbalance of NE levels. Therapeutic strategies to boost levels of protective antiproteases such as A1AT in the lung remain an attractive research strategy to limit the damage from excess protease activity. microRNAs are small non-coding RNA molecules that bind specific cognate sequences to inhibit expression of target mRNAs. The inhibition of miRNAs which target the SERPINA1 (A1AT-encoding gene) mRNA represents a novel therapeutic approach for CF inflammation. This could involve the delivery of antagomirs that bind and sequester the target miRNA, or target site blockers that bind miRNA recognition elements within the target mRNA to prevent miRNA interaction. Therefore, miRNA targeted therapies offer an alternative strategy to drive endogenous A1AT production and thus supplement the antiprotease shield of the CF lung. 


Vertex Pharmaceuticals VIA program 2018

Horizon 2020 (MSCA-IF award 707771 GENDER-CF)

Alpha-1 Foundation Postdoctoral Fellowship 2019

Vertex Pharmaceuticals



The original article is available at

Published Citation

Hunt AMD, Glasgow AMA, Humphreys H, Greene CM. Alpha-1 antitrypsin-a target for microRNA-based therapeutic development for cystic fibrosis. Int J Mol Sci. 2020;21(3):836.

Publication Date

28 January 2020

PubMed ID



  • Beaumont Hospital
  • Clinical Microbiology
  • Undergraduate Research
  • Medicine




  • Published Version (Version of Record)