siRNAzos: A New Class of Azobenzene‐Containing siRNAs that Can Photochemically Regulate Gene Expression

Abstract Fine‐tuning the activity of short‐interfering RNAs (siRNAs) with light could help overcome several obstacles related to potency, delivery, and off‐target effects. In this study, we chemically modify siRNAs that contain azobenzene derivative spacers within the sense strand. These molecules are called siRNAzos and they are successfully accommodated within the RNAi pathway as measured by gene‐silencing dose‐dependent knockdown. In addition to its RNAi biocompatibility, we are able to photochemically control the activity of the siRNAzos that contain the azobenzene within the central region of the sense strand. We demonstrate it is possible to both inactivate and reactivate several siRNAzos with ultraviolet and visible light, respectively.