Cholesterol-Modified Caged siRNAs for Photoregulating Exogenous and Endogenous Gene Expression

siRNA has been widely applied in research and drug development due to its sequence-specific gene silencing ability. However, how to spatiotemporally control its function is still one of its challenges. Light, a fast and noninvasive trigger, is a promising tool for spatiotemporal control of gene expression. Here, we designed and synthesized a new series of caged siRNAs modified with single cholesterol at the 5′ terminal of antisense strand RNA through a photolabile linker (Chol-PL-siRNAs). We demonstrated that these caged siRNAs were successfully used to photochemically regulate both exogenous (<i>firefly luciferase</i> and <i>gfp</i>) and endogenous gene expression (mitotic kinesin-5, <i>Eg5</i>) in cells