title: Pharmacology of Antisense Drugs.
abstract: Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.
authors.affiliation: Ionis Pharmaceuticals, Carlsbad, California 92010; email: fbennett@isisph.com.
authors.forename: C Frank
authors.initials: CF
authors.lastname: Bennett
authors.affiliation: Ionis Pharmaceuticals, Carlsbad, California 92010; email: fbennett@isisph.com.
authors.forename: Brenda F
authors.initials: BF
authors.lastname: Baker
authors.affiliation: Ionis Pharmaceuticals, Carlsbad, California 92010; email: fbennett@isisph.com.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Pham
authors.affiliation: Ionis Pharmaceuticals, Carlsbad, California 92010; email: fbennett@isisph.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Swayze
authors.affiliation: Ionis Pharmaceuticals, Carlsbad, California 92010; email: fbennett@isisph.com.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Geary
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology; D012326:RNA Splicing / Q000187:drug effects / Q000502:physiology
chemical_list: D016376:Oligonucleotides, Antisense
keywords: RNA; RNA interference; RNA splicing; RNase H; antisense oligonucleotides; eteplirsen; mipomersen; nusinersen; oligonucleotide; patisiran