RNA Interference Controlled by Light of Variable Wavelength

Known molecular, “caged” siRNAs are activated by UV light. Since the light of this type is toxic to cells, the uncaging can cause undesired side effects. A modular, molecular system for designing siRNAs is reported, which can be activated by non‐toxic light in live cells. For example, siRNAs responsive to green and red light are described. The uncaging is mediated by ¹O₂ photogenerated on a photosensitizer, which is attached to the 3′‐terminus of the lagging strand. The 5′‐terminus of the guide strand is alkylated (“caged”) with a 9‐anthracenyl residue. The latter fragment reacts with the ¹O₂ with formation of the free (uncaged) 5′‐OH terminus. Simultaneously with the uncaging the photosensitizer is bleached and no more ¹O₂ is generated after this process is completed. The photoactivation of the siRNAs described here is not toxic to cells.