Noncoding RNA therapeutics - challenges and potential solutions

Over the past decade, several RNA-based therapies have gained FDA approval. Additional noncoding RNA (ncRNA)-based therapeutic approaches - targeting microRNAs and long ncRNAs - are now also gaining interest. Here, Calin and co-authors assess the hurdles facing the clinical translation of ncRNA-based therapeutics and highlight promising emerging solutions to address these issues. Therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), represents an attractive approach for the treatment of cancers, as well as many other diseases. Over the past decade, substantial effort has been made towards the clinical application of RNA-based therapeutics, employing mostly antisense oligonucleotides and small interfering RNAs, with several gaining FDA approval. However, trial results have so far been ambivalent, with some studies reporting potent effects whereas others demonstrated limited efficacy or toxicity. Alternative entities such as antimiRNAs are undergoing clinical testing, and lncRNA-based therapeutics are gaining interest. In this Perspective, we discuss key challenges facing ncRNA therapeutics - including issues associated with specificity, delivery and tolerability - and focus on promising emerging approaches that aim to boost their success.

Automated summary

In recent years, RNA-based therapies have gained FDA approval, but there are still challenges in targeting ncRNAs. Therapeutic targeting of noncoding RNAs has the potential to become a new approach for treating diseases such as cancer.