Precise control of transgene expression remains a challenge in engineering primary cells for diverse applications. We developed DIAL, a promoter editing framework that transmits transient inputs into stable setpoints of expression in primary cells and human induced pluripotent stem cells, paving the way for predictable programming of gene circuits in therapeutically relevant cells.
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References
Cabrera, A. et al. The sound of silence: transgene silencing in mammalian cell engineering. Cell Syst. 13, 950–973 (2022). A review article that presents challenges in engineering stable expression in mammalian cells.
Donahue, P. S. et al. The COMET toolkit for composing customizable genetic programs in mammalian cells. Nat. Commun. 11, 779–789 (2020). This paper reports the development of the synthetic zinc-finger transcription factors and promoters in mammalian cells.
Wang, N. B. et al. Proliferation history and transcription factor levels drive direct conversion to motor neurons. Cell Syst. 16, 101205–101220 (2025). This paper presents how levels of native transcription factors influence cell-fate programming.
Li, H.-S. et al. Multidimensional control of therapeutic human cell function with synthetic gene circuits. Science 378, 1227–1234 (2022). This paper reports the development of new ligand-inducible, synthetic zinc-finger transcription factors in mammalian cells.
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This is a summary of: Kabaria, S. R. et al. Programmable promoter editing for precise control of transgene expression. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02854-y (2025).
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Promoter editing generates stable setpoints of gene expression. Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02875-7
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DOI: https://doi.org/10.1038/s41587-025-02875-7
