title: RNA therapeutics: beyond RNA interference and antisense oligonucleotides.
abstract: Here, we discuss three RNA-based therapeutic technologies exploiting various oligonucleotides that bind to RNA by base pairing in a sequence-specific manner yet have different mechanisms of action and effects. RNA interference and antisense oligonucleotides downregulate gene expression by inducing enzyme-dependent degradation of targeted mRNA. Steric-blocking oligonucleotides block the access of cellular machinery to pre-mRNA and mRNA without degrading the RNA. Through this mechanism, steric-blocking oligonucleotides can redirect alternative splicing, repair defective RNA, restore protein production or downregulate gene expression. Moreover, they can be extensively chemically modified to acquire more drug-like properties. The ability of RNA-blocking oligonucleotides to restore gene function makes them best suited for the treatment of genetic disorders. Positive results from clinical trials for the treatment of Duchenne muscular dystrophy show that this technology is close to achieving its clinical potential.
authors.affiliation: AVI BioPharma, 3450 Monte Villa Parkway, Bothell, Washington 98021, USA. rkole@avibio.com
authors.forename: Ryszard
authors.initials: R
authors.lastname: Kole
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Krainer
authors.forename: Sidney
authors.initials: S
authors.lastname: Altman
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D060172:Morpholinos / Q000235:genetics / Q000627:therapeutic use; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics; D009223:Myotonic Dystrophy / Q000188:drug therapy / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D054735:Phosphorothioate Oligonucleotides / Q000235:genetics / Q000627:therapeutic use; D034622:RNA Interference / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017086:beta-Thalassemia / Q000188:drug therapy / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D060172:Morpholinos; D020319:Oligodeoxyribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D012333:RNA, Messenger; D034741:RNA, Small Interfering