Photoregulation of Gene Expression with Amantadine-modified Caged siRNAs Through Host/Guest Interaction

Chemistry : a European Journal
Jinhao ZhangXinjing Tang

Abstract

RNA interference (RNAi) is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of siRNA activity, especially using light activation, is a potential method to regulate target gene expression and functions. Here, a series of photolabile siRNAs with amantadine modification were rationally designed and developed through host/guest interaction of amantadine and β-cyclodextrin derivatives to enhance the blocking effect of siRNA binding and/or processing. These caged siRNAs with amantadine modification at the 5'end of antisense-strand RNA were efficiently inactivated due to the host/guest interaction of amantadine and β-cyclodextrin. Photomodulation of gene silencing activity of these amantadine-modified caged siRNAs targeting both exogenous and endogenous genes was successfully achieved with low leaking activity, which indicated that host/guest interaction could be a new strategy for developing new caged siRNAs for gene photoregulation.

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Citations

Jan 13, 2021·Chembiochem : a European Journal of Chemical Biology·Qian WangXinjing Tang
Sep 18, 2021·Organic & Biomolecular Chemistry·Jun-Ichi Mihara, Kenzo Fujimoto
Nov 6, 2021·Chemical Society Reviews·Kristie E Darrah, Alexander Deiters

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