Synthesis and Evaluation of Caged siRNA with Terminal Single Vitamin E Modification

RNA-induced gene silencing has been widely applied as a powerful research tool in drug development due to its sequence-specific degradation of target mRNA. Conditional regulation of gene functions with small interfering RNAs (siRNAs) is highly useful, especially when specific gene expression regulation with spatiotemporal resolution and amplitude is desired. Here, the synthesis of a series of new caged siRNAs with vitamin E (vitE) modification and/or a single photolabile linker at the 5' terminal is described. Their capability of photolysis was investigated by PAGE gel analysis. Then, a dual reporter firefly/renilla luciferase assay with siQuant vectors and GFP/RFP reporter genes was applied to show the effect of vitE-modified caged and non-caged siRNAs on gene expression. The intracellular distribution and cellular uptake pathways of caged siRNAs are also discussed. © 2016 by John Wiley & Sons, Inc.