Photochemically Triggered,\nTransient, and Oscillatory\nTranscription Machineries Guide Temporal Modulation of Fibrinogenesis

Photochemically triggered, transient, and temporally\noscillatory-modulated\ntranscription machineries are introduced. The resulting dynamic transcription\ncircuits are implemented to guide photochemically triggered, transient,\nand oscillatory modulation of thrombin toward temporal control over\nfibrinogenesis. One system describes the assembly of a reaction module\nleading to the photochemically triggered formation of an active transcription\nmachinery that, in the presence of RNase H, guides the transient activation\nof thrombin toward fibrinogenesis. A second system introduces photochemical\ntriggering of a reaction circuit consisting of two coupled transcription\nmachineries, leading to the temporally oscillatory formation and depletion\nof an intermediate reaction product. The concept is applied to develop\na photochemically triggered transcription circuit that, in the presence\nof RNase H, leads to the oscillatory generation of an intermediate\nanti-thrombin aptamer-modified product. The oscillating aptamer-modified\nproduct induces the rhythmic inhibition of thrombin, accompanied by\nthe cyclic activation and deactivation of the fibrinogenesis process.\nThe operation of the transient and oscillatory-modulated transcription\nmachinery reaction circuits is accompanied by computational kinetic\nmodels, allowing to predict the dynamic behaviors of the system under\ndifferent auxiliary conditions. The phototriggered transient transcription\nmachinery and oscillatory circuit-guided fibrinogenesis is examined\nunder physiological-like conditions and within a human plasma environment.