Photoswitches for controllable RNA binding: a future approach in the RNA-targeting therapy

Abstract

RNA is an emerging drug target that opens new perspectives in the treatment of viral and bacterial infections, cancer and a range of so far incurable genetic diseases. Among the...

Small-molecule photoswitches for fluorescence bioimaging: engineering and applications

“…Numerous examples report the use of small-molecule photoswitches as non-fluorescent binders, in which the reactivity of the probe depends on the isomeric state. 72,73 In contrast, there are only a limited number of examples combining photoswitching and biosensing with fluorescence imaging. From an engineering perspective, two main approaches can be identified, either by exploiting the intrinsic properties of the switch or by appending a well-established binding or reactive group to the scaffold.…”

Recent Synthetic Biology Approaches for Temperature- and Light-Controlled Gene Expression in Bacterial Hosts

“…Photoswitchable molecules have two isomeric states that can be interconverted through irradiation with different light inputs at different wavelengths [ 64 ], which enables reversible genetic control. Although challenging, controlling gene expression with a photoswitchable riboswitch ligand [ 65 , 66 ] offers the opportunity to reversibly regulate artificial genetic circuits [ 67 ]. Recently, in vivo demonstrations of stiff-stilbene- [ 45 ] and azobenzene-based [ 44 ] photoswitchable ligands were reported, showing the regulation of RNA-controlled gene expression in E. coli ( Figure 3 B).…”

Reversible Control of RNA Splicing by Photoswitchable Small Molecules

“…RNA executes complex functions at specific times and localizations; therefore, precise control over RNA dynamics is in high demand not only for deciphering the molecular mechanism underneath RNA-regulated systems but also for pharmacological application or diagnosis. , For this purpose, light-mediated approaches are invaluable because of their intrinsic spatiotemporal resolution with minimal invasive action. Although recent years have witnessed a growing fascination with using these tools to interrogate biological processes, , the toolkit for RNA photocontrol remains vastly underexplored. , In this context, modified oligonucleotides with either photoswitches − or photocages − have been effective; however, they require alterations in the native structure and suffer from metabolic degradation as well as uptake issues, above all, for crossing the blood–brain barrier. There are also a few examples of riboswitches or RNA aptamers capable of selectively interacting with a conformer of a photoswitchable ligand , or photoreceptors .…”

“…Although recent years have witnessed a growing fascination with using these tools to interrogate biological processes, 7,8 the toolkit for RNA photocontrol remains vastly underexplored. 6,9 In this context, modified oligonucleotides with either photoswitches 10−15 or photocages 16−18 have been effective; however, they require alterations in the native structure and suffer from metabolic degradation as well as uptake issues, above all, for crossing the blood−brain barrier. There are also a few examples of riboswitches or RNA aptamers 6 capable of selectively interacting with a conformer of a photoswitchable ligand 19,20 or photoreceptors.…”