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Synthetic dynamic transcription frameworks and their applications

Nature Chemistry volume 18, pages 227–245 (2026)Cite this article

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Abstract

Biological transcription uses dynamic machinery modulated by transcription factors and auxiliary environmental cues to control multiple biological processes. Misregulation of the transcription machinery leads to diverse genetic disorders and diseases. Here we discuss the application of DNA nanostructures and circuits in developing synthetic in vitro transcription frameworks that mimic dynamic features, such as switchable blockage of transcription by topological barriers, transcription machineries revealing transient dissipative kinetics, and bistable programs or oscillatory transcription circuits driven by feedback loops, paving the way to exploring and validating mechanisms in native transcription and their potential biological applications. Possible applications of the transcription frameworks for sensing, and future perspectives for autonomous therapeutics and the design of artificial cells, are discussed.

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Fig. 1: Dynamic temporal modulation of transcription frameworks by auxiliary triggers regulating the outputs.
Fig. 2: Switchable transcription machineries.
Fig. 3: Alternative platforms operating dissipative transcription machineries.
Fig. 4: Transcription machinery-mediated intercommunication of two transient NAD+-driven ligation–digestion circuits.
Fig. 5: Temporal modulation of biological transformations and nanostructures by transient transcription machineries.
Fig. 6: Bistable transcription regulatory networks.
Fig. 7: Oscillatory transcription circuits.
Fig. 8: Transcription machineries as functional modules for sensing.

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Acknowledgements

This research is supported by the Israel Science Foundation (grant 2049/20).

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  1. Jiantong Dong

    Present address: College of Chemistry and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, People’s Republic of China

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  1. Institute of Chemistry and Center for Nanoscience and Nanotechnology, Hebrew University of Jerusalem, Jerusalem, Israel

    Jiantong Dong & Itamar Willner

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J.D. and I.W. contributed to discussions and co-wrote the paper.

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Dong, J., Willner, I. Synthetic dynamic transcription frameworks and their applications. Nat. Chem. 18, 227–245 (2026). https://doi.org/10.1038/s41557-025-02046-w

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