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.

Links

Publisher Full Text

Authors

Kole R, Krainer AR, Altman S

Institution

AVI BioPharma, 3450 Monte Villa Parkway, Bothell, Washington 98021, USA. rkole@avibio.com

Source

Nature reviews. Drug discovery 11:2 2012 Feb pg 125-40

MeSH

Alternative Splicing
Animals
Anti-Bacterial Agents
Antiviral Agents
Gene Expression
Humans
Morpholinos
Muscular Dystrophy, Duchenne
Myotonic Dystrophy
Oligodeoxyribonucleotides, Antisense
Phosphorothioate Oligonucleotides
RNA Interference
RNA, Messenger
RNA, Small Interfering
beta-Thalassemia

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

22262036