Photochemical Regulation of Gene Expression Using Caged siRNAs with Single Terminal VitaminE Modification

被引：55

作者：

Ji, Yuzhuo ^{[1
]}

Yang, Jiali ^{[1
]}

Wu, Li ^{[1
]}

Yu, Lijia ^{[1
]}

Tang, Xinjing ^{[1
]}

机构：

[1] Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2016年 / 55卷 / 06期

基金：

中国国家自然科学基金;

关键词：

caged oligonucleotides; gene regulation; photoactivation; siRNA; vitaminE modification; RNA INTERFERENCE; OPTOCHEMICAL CONTROL; LIGHT; ZEBRAFISH; OLIGONUCLEOTIDES; CONJUGATION; PHOSPHATE; CLEAVAGE;

D O I：

10.1002/anie.201510921

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Caged siRNAs with a single photolabile linker and/or vitaminE (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.

引用

页码：2152 / 2156

页数：5

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