Brief considerations on targeting RNA with small molecules

For more than three decades, RNA has been known to be a relevant and attractive macromolecule to target but figuring out which RNA should be targeted and how remains challenging. Recent years have seen the confluence of approaches for screening, drug optimization, and target validation that have led to the approval of a few RNA-targeting therapeutics for clinical applications. This focused perspective aims to highlight — but not exhaustively review — key factors accounting for these successes while pointing at crucial aspects worth considering for further breakthroughs.