gene functions. Conditional control of small interfering RNA (siRNA) activity, especially using light activation, is a potential method for regulating target gene expression and functions. In this study, a series of photolabile siRNAs with amantadine modification have been rationally designed and developed through host–guest interactions between amantadine and β‐cyclodextrin derivatives to enhance the
CagedsiRNAs with a single photolabile linker and/or vitaminE (vitE) modification at the 5′ terminal were rationally designed and synthesized. These virtually inactive cagedsiRNAs were successfully used to photoregulate both firefly luciferase and GFP geneexpression in cells with up to an 18.6‐fold enhancement of gene silencing activity, which represents one of the best reported photomodulation