Therapeutic strategies to target the epitranscriptomic machinery

Altered RNA modification patterns and dysregulated expression of epitranscriptomic machinery proteins (EMPs) have been causatively correlated with several diseases. Modulation of EMP gene expression has shown promise in reversing disease-associated phenotypes, making EMPs attractive therapeutic targets.

Various therapeutic strategies, including small-molecule modulators, proteolysis-targeting chimeras, and molecular tools for site-specific engineering of RNA modifications, have been introduced to modulate EMPs and RNA modifications themselves and are currently being investigated to enrich the physician’s armamentarium. At the forefront of research are small-molecule inhibitors of the key players involved in the N⁶-methyladenosine RNA modification, with an inhibitor of methyltransferase 3 in clinical trials. Preclinical studies have also demonstrated proof-of-concept for the other approaches, raising expectations for this exciting new frontier of therapy.