Emerging applications and prospects of NFκB decoy oligodeoxynucleotides in managing respiratory diseases

Datsyuk JK 1 , Paudel KR 2 , Rajput R 1 , Kokkinis S 1 , El Sherkawi T 1 , Singh SK 3 Show all authors , Gupta G 4 , Chellappan DK 5 , Yeung S 1 , Hansbro PM 6 , Oliver BGG 7 , Santos HA 8 , Dua K 9 , De Rubis G 10

Affiliations 

  • 1 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia
  • 2 Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
  • 3 Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India
  • 4 Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India; School of Pharmacy, Suresh Gyan Vihar University, Jagatpura 302017, Jaipur, India
  • 5 Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, 57000, Malaysia
  • 6 Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, 2007, Australia
  • 7 Woolcock Institute of Medical Research, Macquarie University, Sydney, New South Wales, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW, 2007, Australia
  • 8 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV, Groningen, the Netherlands; W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV, Groningen, the Netherlands
  • 9 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India. Electronic address: Kamal.Dua@uts.edu.au
  • 10 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia. Electronic address: Gabriele.DeRubis@uts.edu.au
Chem Biol Interact, 2023 Nov 01;385:110737.
PMID: 37774998 DOI: 10.1016/j.cbi.2023.110737

Abstract

Chronic respiratory diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD) have been a burden to society for an extended period. Currently, there are only preventative treatments in the form of mono- or multiple-drug therapy available to patients who need to utilize it daily. Hence, throughout the years there has been a substantial amount of research in understanding what causes inflammation in the context of these diseases. For example, the transcription factor NFκB has a pivotal role in causing chronic inflammation. Subsequent research has been exploring ways to block the activation of NFκB as a potential therapeutic strategy for many inflammatory diseases. One of the possible ways through which this is probable is the utilisation of decoy oligodeoxynucleotides, which are synthetic, short, single-stranded DNA fragments that mimic the consensus binding site of a targeted transcription factor, thereby functionally inactivating it. However, limitations to the implementation of decoy oligodeoxynucleotides include their rapid degradation by intracellular nucleases and the lack of targeted tissue specificity. An advantageous approach to overcome these limitations involves using nanoparticles as a vessel for drug delivery. In this review, all of those key elements will be explored as to how they come together as an application to treat chronic inflammation in respiratory diseases.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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