title: Photochemical Regulation of Gene Expression Using Caged siRNAs with Single Terminal Vitamin E Modification.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191, China.
authors.forename: Yuzhuo
authors.identifier: http://orcid.org/0000-0001-7108-8415
authors.initials: Y
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191, China.
authors.forename: Jiali
authors.identifier: http://orcid.org/0000-0002-7255-4403
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191, China.
authors.forename: Lijia
authors.identifier: http://orcid.org/0000-0003-3059-7621
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Rd., Beijing, 100191, China. xinjingt@bjmu.edu.cn.
authors.forename: Xinjing
authors.identifier: http://orcid.org/0000-0002-9959-1167
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D048888:Fireflies; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D020868:Gene Silencing / Q000187:drug effects / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics*; D008027:Light; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics*; D015394:Molecular Structure; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014810:Vitamin E / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D034741:RNA, Small Interfering; D014810:Vitamin E; D049452:Green Fluorescent Proteins; D049409:Luciferases, Firefly
keywords: caged oligonucleotides; gene regulation; photoactivation; siRNA; vitamin E modification