Perspectives in MicroRNA Therapeutics

RNA-based therapeutics hold significant potential as promising treatment options for human disease. In the past 20 years, advances in the RNA field have identified several novel RNAbased therapies that are currently under clinical investigation, including antisense oligonucleotides, small interfering RNA (siRNA), and microRNA. By targeting RNA and modulating human biology at the molecular level, these new technologies have allowed drug-discovery efforts to focus on a broad range of disease targets once deemed to be “undruggable.” Leading RNA biotechnology companies have since expanded the target space and generated multiple clinical candidates characterized by improved target specificity, improved drug safety, and demonstrated efficacy in patients. These companies have traditionally focused on targeting specific genes relevant to the disease indication through the control of protein synthesis at the RNA level. More recently, drug discovery researchers are attempting to regulate entire networks of genes through the modulation of a single microRNA. Targeting microRNAs with either oligonucleotide inhibitors, namely anti-miRs, or miR-mimics (doublestranded oligonucleotides that replace microRNA function), provides a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways (see Figure 1).