Photochemical Regulation of Gene Expression Using Caged siRNAs with Single Terminal Vitamin E Modification
Yuzhuo Ji
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
These authors contributed equally to this work.
Search for more papers by this authorJiali Yang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Li Wu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
Search for more papers by this authorDr. Lijia Yu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
Search for more papers by this authorCorresponding Author
Prof. Xinjing Tang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
Search for more papers by this authorYuzhuo Ji
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
These authors contributed equally to this work.
Search for more papers by this authorJiali Yang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Li Wu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
Search for more papers by this authorDr. Lijia Yu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
Search for more papers by this authorCorresponding Author
Prof. Xinjing Tang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191 China
Search for more papers by this authorAbstract
Caged siRNAs with a single photolabile linker and/or vitamin E (vitE) modification at the 5′ terminal were rationally designed and synthesized. These virtually inactive caged siRNAs were successfully used to photoregulate both firefly luciferase and GFP gene expression in cells with up to an 18.6-fold enhancement of gene silencing activity, which represents one of the best reported photomodulation of gene silencing efficiencies to date. siRNA tracking and vitE competition experiments indicated that the inactivity of vitE-modified siRNAs was not due to the bulky moiety of vitE; rather, the involvement of vitE-binding proteins has a large contribution to caged siRNA inactivation by preventing the dissociation of siRNA/lipo complexes and/or siRNA release. Further patterning experiments revealed the ability to spatially regulate gene expression through simple light irradiation.
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