RNA therapeutics: Beyond RNA interference and antisense oligonucleotides

By R. Kole, Adrian R. Krainer, S. Altman. Nature reviews. Drug discovery, 2012

1,108 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d5f72af46d1f0415df3743dab937de91da7a616f

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In Genetics

1. Guangdi Li
2. Tom Misteli

In Molecular Biology

1. R. Juliano
2. Guangdi Li
3. Tom Misteli
4. M. Salton
5. H. Kimura
6. Peter R. Cook
7. V. Corces
8. Angus I. Lamond

Citations in the corpus

• Approved Antiviral Drugs over the Past 50 Years (2016, background): “, RNA interference [RNAi] [467]), the development of successful antiviral treatments remains a challenge.”
• Small molecule modulators of pre-mRNA splicing in cancer therapy (2015, background): “We focus our discussion on the modulation of specific splicing events and do not include approaches to restore global splicing patterns nor the use of antisense-based approaches to splicing regulation [18].”
• The delivery of therapeutic oligonucleotides (2016, background): “In doing so they can modify splicing in various ways such as promoting alternative use of exons, exon exclusion or exon inclusion (20).”