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Updated: May 16, 2025

Predicting Gene Silencing Through the Spatiotemporal Control of siRNA Release from Photo-responsive Polymeric Nanocarriers
Published on: July 21, 2017
Harnessing Molecular Recognition for Small-Molecule-Mediated Reversible Photochemical Control Over mRNA Translation
Shaifaly Parmar1, Logan Tenney1, Xiao Liang1
1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
Abstract:
Chemical probes that control the function of complex RNA molecules offer unique opportunities to interrogate biological systems. In this study, we demonstrate that a small molecule ligand selectively recognizes and undergoes traceless, reversible photocrosslinking to PreQ1 RNA aptamers. This effect is selective and dependent on both the chemical structure and RNA sequence/structure. A homogeneously modified, caged mRNA construct containing a PreQ1 aptamer and an eGFP or wild type p53 coding sequence displayed repressed translation in vitro or in cells until irradiated with 302 nm light, resulting in cleavage of the photocage and restoration of translation. This method demonstrates for the first time that aptamer-based molecular recognition of a small molecule ligand can be used to precisely and photochemically activate the translation of a complex mRNA in cells.
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