Unbound MEDLINE

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.

Links

  • Publisher Full Text
  • Authors

    Kole R, Krainer AR, Altman S

    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