Targeting microRNAs for immunomodulation

- microRNAs are critical for immune regulation and constitute interesting drug targets.
- Drugs targeting RNAs work in humans.
- Delivery of nucleic acid-based drugs remains a bottle-neck for immunomodulation through miRNAs.
- Small molecules may be a viable alternative to nucleic acid-based drugs to modulate miRNA function.

microRNAs (miRNA) are small regulatory RNAs exerting pleiotropic functions in virtually any immune cell-type. Dozens of miRNAs with a known function in the immune system constitute interesting drug targets for immunomodulation. Chemical modifications of nucleic acid-based miRNA mimics and inhibitors largely solved instability issues but delivery to immune cells remains a major challenge. However, recent success targeting the acidic tumor microenvironment is very promising for inflammatory diseases. Moreover, small molecules are being explored as an interesting alternative. Although RNA is often considered 'undruggable' by small molecules recent progress modulating miRNA function through small molecules is encouraging. Computational approaches even allow predictions about specific small molecule/RNA interactions. Finally, recent clinical success demonstrates that drugs targeting RNAs work in humans.