Figure 2.

Timeline of major developments in the RNA-targeting field. The history of drugging RNA is tied closely with molecular biology discoveries (DNA/RNA structural determination). Antibacterials that targeted RNA preceded the first investigations into antisense oligonucleotides. However, FDA approvals of antisense oligonucleotides increased upon completion of the human genome project. Recent developments, such as the use of rational design-based approaches, the initiation of clinical trials for small molecule drugs treating spinal muscular atrophy (SMA), and the first report of ribonuclease targeting chimeras (RIBOTACs), demonstrate the rapid development of small molecules targeting RNA. These advancements provide a convincing argument to turn our focus to the druggable transcriptome.