An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies

• Recent human clinical trial data on RNAi approaches to gene down-regulation for genetic diseases.
• Overview of current anti-microRNA drugs with specific emphasis on application to target Hepatitis C infection.
• Update on the current state of ‘exon skipping’ field for both Duchenne muscular dystrophy and spinal muscular atrophy.

Despite the discovery more than two decades ago that antisense oligonucleotides (ASOs) could be used to modulate protein expression, there have been only two antisense drugs approved for clinical use till date. Despite this low success rate, the antisense field is undergoing resurgence due to the development of more potent and nuclease resistant chemistries, as well as nanoparticle delivery systems that enhance delivery to target tissues. In this review, we introduce the predominant therapeutic strategies in the antisense field whilst highlighting recent clinical findings that demonstrate the significant potential of these approaches for development of novel therapies in several diseases.