TY - JOUR
T1 - Clinical potential of oligonucleotide-based therapeutics in the respiratory system
AU - Moschos, Sterghios A.
AU - Usher, Louise
AU - Lindsay, Mark A.
PY - 2017/1
Y1 - 2017/1
N2 - 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.
AB - 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.
KW - Delivery
KW - MiRNA
KW - Oligonucleotide therapeutics
KW - PNA
KW - PPMO
KW - SiRNA
UR - http://www.scopus.com/inward/record.url?scp=84993940278&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.pharmthera.2016.10.009
U2 - 10.1016/j.pharmthera.2016.10.009
DO - 10.1016/j.pharmthera.2016.10.009
M3 - Article
AN - SCOPUS:84993940278
SN - 0163-7258
VL - 169
SP - 83
EP - 103
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
ER -