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) 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 large 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 has been largely 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.