Clinical potential of oligonucleotide-based therapeutics in the respiratory system

Moschos, S.A., Usher, L. and Lindsay, M.A. 2017. Clinical potential of oligonucleotide-based therapeutics in the respiratory system. Pharmacology and Therapeutics. 169, pp. 83-103. https://doi.org/10.1016/j.pharmthera.2016.10.009

TitleClinical potential of oligonucleotide-based therapeutics in the respiratory system
AuthorsMoschos, S.A., Usher, L. and Lindsay, M.A.
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.

KeywordsOligonucleotide therapeutics, siRNA, miRNA, PNA, PPMO, delivery
JournalPharmacology and Therapeutics
Journal citation169, pp. 83-103
ISSN0163-7258
Year2017
PublisherElsevier
Accepted author manuscript
Digital Object Identifier (DOI)https://doi.org/10.1016/j.pharmthera.2016.10.009
Publication dates
Published online19 Oct 2016
Published19 Oct 2016

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