The journey of noncoding RNA from bench to clinic

Abstract

The discovery of noncoding RNA (ncRNA) in the 90s completely changed our understanding of gene regulation. The ncRNAs specialize in regulating the gene expression, which enables them to induce a remarkable change in cellular pathways. The ncRNAs are categorized as small (<200 nucleotides) and long ncRNA (>200 nucleotides). The small ncRNAs are further classified as miRNAs, piwi-interacting RNAs (piRNAs), small interfering RNAs (siRNAs), and small nucleolar RNAs (snoRNAs). Both miRNAs and siRNAs silence gene expression by binding to their target mRNA but follow different mechanisms. piRNAs are responsible for bringing about transposon repression, and snoRNAs are mainly involved in the modification of rRNAs. The lncRNAs have diverse functions that range from chromatin modification to acting as a precursor of miRNAs to binding to mRNAs and blocking their translation. With such important functions in their repertoire, tightly regulated tissue-specific expression and differential expression in diseased conditions, the potential of ncRNAs as therapeutic targets and biomarkers is waiting to be exploited. As per the ClinicalTrials database of NLM, the number of clinical trial studies recorded for miRNAs, siRNAs, and lncRNAs are 861, 67, and 39, respectively. The siRNA therapeutic, Patisiran, became the first ncRNA to receive FDA approval for the treatment of a rare polyneuropathy in 2018. Miravirsen, an inhibitor of miR-122 is the first miRNA therapeutic drug, which is currently in multiple phase 2 clinical trials for the treatment of Hepatitis C. The lncRNA PCA3 was approved as a biomarker for prostate cancer in 2012. This chapter discusses the journey of ncRNA from bench to clinic with a few specific examples elaborating on the basic research involved in identifying them as biomarkers or therapeutic targets and bottlenecks in their clinical use. � 2021 Elsevier Inc. All rights reserved.