Non-coding RNAs as drug targets

Masayuki Matsui & David R. Corey, Nature Reviews Drug Discovery (2016), doi:10.1038/nrd.2016.117

The ability of ncRNAs to control gene expression makes them potential targets for drug development. However, the drug discovery process is never easy. Uncertainty about how ncRNAs function (and even whether they have a function) makes lead identification and development even more challenging.

Expanded repeats within introns, 3ʹ untranslated regions (UTRs) or 5ʹ UTRs can produce toxic mutant RNAs (for example, as seen in myotonic dystrophy) or affect the production of proteins (for example, as seen in Friedreich ataxia and Fragile X syndrome).

Case study: Friedreich ataxia.Our laboratory has targeted steric-block locked nucleic acid (LNA) ASOs and duplex RNAs to the expanded GAA repeat in cells derived from patients with Friedreich ataxia. These compounds reduce R‑loop formation and increase frataxin mRNA and protein levels to those found in wild-type cells.

 Non-coding RNAs as drug targets