Targeting RNA with small molecules-A safety perspective

RNA is a major player in cellular function, and consequently can drive a number of disease pathologies. Over the past several years, small molecule-RNA targeting (smRNA targeting) has developed into a promising drug discovery approach. Numerous techniques, tools, and assays have been developed to support this field, and significant investments have been made by pharmaceutical and biotechnology companies. To date, the focus has been on identifying disease validated primary targets for smRNA drug development, yet RNA as a secondary (off) target for all small molecule drug programs largely has been unexplored. In this perspective, we discuss structure, target, and mechanism-driven safety aspects of smRNAs and highlight how these parameters can be evaluated in drug discovery programs to produce potentially safer drugs.

Automated summary

RNA plays a vital role in cellular function and can contribute to various diseases. Small molecule-RNA targeting has emerged as a promising approach for drug discovery, with significant investments from pharmaceutical and biotechnology companies. However, the exploration of RNA as a secondary target in small molecule drug programs has been limited. This perspective discusses the safety aspects of smRNAs based on structure, target, and mechanism, and suggests evaluating these parameters to develop potentially safer drugs.