A Genetically Encoded RNA Photosensitizer for Targeted Cell Regulation

Abstract

Genetically encoded RNA devices have emerged for various cellular applications in imaging and biosensing, but their functions as precise regulators in living systems are still limited. Inspired by protein photosensitizers, we propose here a genetically encoded RNA aptamer based photosensitizer (GRAP). Upon illumination, the RNA photosensitizer can controllably generate reactive oxygen species for targeted cell regulation. The GRAP system can be selectively activated by endogenous stimuli and light of different wavelengths. Compared with their protein analogues, GRAP is highly programmable and exhibits reduced off-target effects. These results indicate that GRAP enables efficient noninvasive target cell ablation with high temporal and spatial precision. This new RNA regulator system will be widely used for optogenetics, targeted cell ablation, subcellular manipulation, and imaging.

Genetically encoded RNA nanodevices for cellular imaging and regulation

“…170 Our group has also recently demonstrated a genetically encoded RNA aptamer-based photosensitizer system, termed GRAP, for targeted cell regulation in both prokaryotic and eukaryotic cells. 171 These photosensitizers can generate reactive oxygen species (ROS) upon light irradiation and lead to cell structure damage and photodynamic therapy. In this GRAP system, a DNB aptamer was used to selectively bind with a dinitroaniline quencher and separate it from the attached photosensitizer, which can further result in the restoration of the ROS generation (Fig.…”

“…With these further improvements, we believe, in the near future, genetically encoded RNA nanodevices will perform real intelligent intracellular diagnostics and therapeutics in a way, as good as, if not better than, their natural RNA and protein rivals. 171 (b) Schematic of a target-activated photosensitizer RNA nanodevice. The addition of a target RNA refolds the DNB aptamer, which can further lead to the reactivation of the PS.…”

“…The addition of a target RNA refolds the DNB aptamer, which can further lead to the reactivation of the PS. 171…”

“…A photosensitizer (PS) is originally quenched by the attached dinitroaniline (DN) quencher. The binding of a DNB aptamer with the DN quencher can restore the PS to generate reactive oxygen species (ROS) upon light irradiation 171. (b) Schematic of a target-activated photosensitizer RNA nanodevice.…”

“…(b) Schematic of a target-activated photosensitizer RNA nanodevice. The addition of a target RNA refolds the DNB aptamer, which can further lead to the reactivation of the PS 171.…”