![]() In addition to these upstream studies into cellular biology, it may be possible for these switches to be developed into therapeutic strategies. There are indeed potentially vast applications for these switches in the field of biology, ranging from boosting studies into cellular pathways to enabling new technologies in synthetic biology. wrote that they hope that these photosensitive switches could be used in the “remote control of protein localisation, cell death, transcriptional programming, and precise base editing”. This is especially promising given that the shining of light is among the least invasive methods of regulating these changes this strategy could potentially be used in conjunction with existing approaches-like small molecules-to effect more specific intracellular changes. could regulate the interactions between these intrabodies and their targets. By incorporating light-mediated ON- and OFF-switches into intrabodies, He et al. I selected this preprint for its complementary and orthogonal nature with other recent advances 1-2, 4 in modulating the conformations of biological constructs. What I like about this preprint: All at once, everything is different used SolarFLARE to drive gene expression, stimulate downstream cellular effects like necroptosis, and even induce base editing using a photoactivable cytosine base editor. By combining the sunbody with the Fast Light- and Activity-Regulated Expression (FLARE) transcription factor system, 5 the authors created the SolarFLARE platform for light-inducible transcriptional activation. used a similar approach to design “sunbodies”, nanobodies that could be activated by light. Having constructed these moonbodies, He et al. Since the dissociation of these moonbodies could be induced simply by shining light on them, the authors sought to answer two questions: first, could the location of their activation be made specific by shining the light on one region while keeping the rest in the dark, and second, could activation be controlled by turning out the lights? Indeed, the authors even demonstrated spatial and temporal selectivity: by shining light on specific regions, they could target one field over another and, by turning the light on and off, they could modulate the moonbodies’ conformations on a timescale of seconds. Using this approach, the authors also made two further moonbodies that targeted other parts of the cell. eventually made an intrabody construct that dissociated well from the nuclear envelope in the presence of light, which they named the “moonbody”. By varying the position of the LOV2 photoswitch, He et al. This was based on the hypothesis that light would induce changes in LOV2’s shape, allowing the authors to visualise the effect of light on the interaction between these intrabodies and its intended target-a nuclear envelope-in live cells. first designed a moonbody by engineering a photoswitch called LOV2 into live cells. Key findings of preprint: shining in the laser light Moonbodies’ and sunbodies’ responses to light. invented a pair of nanobodies that respond to light in seconds-light switches on the sunbody and switches off the moonbody ( Fig. To improve the intrabodies’ response to light, He et al. 1-4 However, these intrabodies are currently limited in their slow response to these stimuli. ![]() Some of these antibodies found within the cell, known as intrabodies, have been engineered to respond to chemical and light changes. Background of preprint: The way things wereĪntibodies-special proteins of the immune system that recognise and bind to foreign species in the body-are incredibly useful tools in biology and medicine.
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