Binding to RNA is not enough—changing its shape is what makes a drug work, study reveals
Why it matters: This research could lead to the design of new, more effective RNA-targeting drugs, potentially impacting billions in pharmaceutical investment.
- Danny Incarnato's team found that while many small molecules bind to RNA, only those that alter its structure have a significant impact on its function, addressing a major gap in drug development.
- RNA molecules can adopt multiple shapes, and effective drugs like mitoxantrone stabilize a specific shape, leading to functional consequences.
- The study proposes a new framework to identify and characterize RNA structure-changing small molecule drugs, aiming to overcome the current low success rate in RNA-targeting drug development, with only one mRNA-targeting drug (risdiplam) currently on the market.
A groundbreaking study led by Danny Incarnato at the University of Groningen reveals that for small-molecule drugs to effectively target RNA, merely binding to it isn't enough; they must actively change its shape. Published in Nature Communications, this research highlights that drugs capable of modulating RNA's structural ensemble, like the cancer drug mitoxantrone, are far more effective in altering RNA function than those that simply bind.
