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 ( firefly luciferase and gfp) and endogenous gene expression (mitotic kinesin-5, Eg5) in cells.