title: Clinical potential of oligonucleotide-based therapeutics in the respiratory system.
abstract: The discovery of an ever-expanding plethora of coding and non-coding RNAs with nodal and causal roles in the regulation of lung physiology and disease is reinvigorating interest in the clinical utility of the oligonucleotide therapeutic class. This is strongly supported through recent advances in nucleic acids chemistry, synthetic oligonucleotide delivery and viral gene therapy that have succeeded in bringing to market at least three nucleic acid-based drugs. As a consequence, multiple new candidates such as RNA interference modulators, antisense, and splice switching compounds are now progressing through clinical evaluation. Here, manipulation of RNA for the treatment of lung disease is explored, with emphasis on robust pharmacological evidence aligned to the five pillars of drug development: exposure to the appropriate tissue, binding to the desired molecular target, evidence of the expected mode of action, activity in the relevant patient population and commercially viable value proposition.
authors: Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, 115 New Cavendish Str., London, W1W 6UW, United Kingdom; Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Ellison Place, Newcastle-Upon-Tyne, NE30 2DR, United Kingdom. Electronic address: sterghios.moschos@northumbria.ac.uk.
authors: Sterghios A
authors: SA
authors: Moschos
authors: Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, 115 New Cavendish Str., London, W1W 6UW, United Kingdom.
authors: Louise
authors: L
authors: Usher
authors: Department of Pharmacy and Pharmacology, Claverton Down, University of Bath, Bath BA2 7AY, United Kingdom.
authors: Mark A
authors: MA
authors: Lindsay
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D012326:RNA Splicing; D022661:RNA, Untranslated / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; D022661:RNA, Untranslated; D012313:RNA
keywords: Delivery; Oligonucleotide therapeutics; PNA; PPMO; miRNA; siRNA