Department of Chemistry, University of Massachusetts, Amherst, MA, 01003, USA.
Angew Chem Int Ed Engl. 2020 Dec 1;59(49):21986-21990. doi: 10.1002/anie.202010106. Epub 2020 Oct 7.
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.
基因编码 RNA 设备已被广泛应用于成像和生物传感等领域，但在活细胞系统中作为精确调控因子的功能仍受到限制。受蛋白质光感受器的启发，我们在这里提出了一种基于基因编码 RNA 适体的光感受器（GRAP）。在光照下，RNA 光感受器可以可控地产生活性氧物质，从而实现靶向细胞调控。GRAP 系统可以被内源性刺激和不同波长的光选择性激活。与它们的蛋白质类似物相比，GRAP 具有高度的可编程性，并且减少了脱靶效应。这些结果表明，GRAP 可以实现高效的非侵入性靶细胞消融，具有高时空精度。这个新的 RNA 调控系统将广泛应用于光遗传学、靶向细胞消融、亚细胞操作和成像等领域。
