Photochemically Triggered, Transient, and Oscillatory Transcription Machineries Guide Temporal Modulation of Fibrinogenesis

Jiantong Dong, Itamar Willner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Photochemically triggered, transient, and temporally oscillatory-modulated transcription machineries are introduced. The resulting dynamic transcription circuits are implemented to guide photochemically triggered, transient, and oscillatory modulation of thrombin toward temporal control over fibrinogenesis. One system describes the assembly of a reaction module leading to the photochemically triggered formation of an active transcription machinery that, in the presence of RNase H, guides the transient activation of thrombin toward fibrinogenesis. A second system introduces photochemical triggering of a reaction circuit consisting of two coupled transcription machineries, leading to the temporally oscillatory formation and depletion of an intermediate reaction product. The concept is applied to develop a photochemically triggered transcription circuit that, in the presence of RNase H, leads to the oscillatory generation of an intermediate anti-thrombin aptamer-modified product. The oscillating aptamer-modified product induces the rhythmic inhibition of thrombin, accompanied by the cyclic activation and deactivation of the fibrinogenesis process. The operation of the transient and oscillatory-modulated transcription machinery reaction circuits is accompanied by computational kinetic models, allowing to predict the dynamic behaviors of the system under different auxiliary conditions. The phototriggered transient transcription machinery and oscillatory circuit-guided fibrinogenesis is examined under physiological-like conditions and within a human plasma environment.

Original languageEnglish
Pages (from-to)2216-2227
Number of pages12
JournalJournal of the American Chemical Society
Volume147
Issue number2
DOIs
StatePublished - 15 Jan 2025

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.

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