Modulation of noncoding RNAs (ncRNAs) and their potential role as therapeutics

Abstract Besides the classical view of RNA as an intermediate carrier of genetic information from the DNA, the protein via the template function of messenger RNA (mRNA), a larger and much more heterogeneous group of noncoding RNAs (ncRNAs) contributes to the regulation of gene expression either by providing structural and functional components (ribosomal RNAs and transfer RNAs) and a panoply of other noncoding RNAs that contribute to the regulation of gene expression through an epigenetic mode of action by modulating mRNA stability. While ncRNAs range in size from short polynucleotides to RNA molecules of >  100 kbp, microRNAs (miRNAs), of 21–23 nucleotides in length, are the most studied ncRNAs due to their capacity to modulate gene expression via RNA interference of activation. Here, we summarize the current achievements in the use of ncRNAs as therapeutic approaches. A brief introduction will present the general picture of ncRNAs in the regulation of gene expression and the subjacent molecular mechanisms. Next, the concept of RNA interference and activation mediated by short RNAs will be discussed. Following this introductory part, the behavior of ncRNAs in different pathologies will be discussed, considering their usefulness both as biomarkers as well as promising therapeutic approaches based on the delivery of ncRNAs being able to modulate gene expression. To cover the latest developments in the field, this chapter will terminate with the presentation of some short-interfering RNA- and short-activating RNA-based therapies that have entered clinical trials and even the marketing phase, proving that decades of research on noncoding RNAs have come to clinical fruition.