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Enabling RNA-compatible synthetic receptors through RNA editing

Nature Reviews Molecular Cell Biology volume 26, page 581 (2025)Cite this article

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Detecting extracellular and intracellular signals and generating appropriate responses is fundamental to biological systems and therapeutic applications. Advancements in synthetic receptors have greatly enhanced our ability to comprehend and manipulate cellular interactions, yet all modular approaches rely on transcription activation, which limits their delivery, timing and applications.

LIDAR demonstrates exceptional versatility in both input sensing and output production. On the input side, LIDAR is compatible with various receptor architectures and enables diverse input sensing. On the output side, LIDAR produces functional proteins capable of controlling cellular processes such as apoptosis. Similarly, it can also interface with synthetic systems, as demonstrated with the retained endoplasmic cleavable secretion (RELEASE) platform, in which a cargo protein is retained in the endoplasmic reticulum and secreted only in response to a specific protease produced by LIDAR. Given its high sensitivity and capacity to distinguish both juxtacrine and paracrine signals, LIDAR further enables synthetic spatial patterning, allowing the programming of multicellular behaviours.

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Authors and Affiliations

  1. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Xiaowei Zhang & Luis S. Mille-Fragoso

  2. Sarafan ChEM-H, Stanford University, Stanford, CA, USA

    Xiaowei Zhang & Luis S. Mille-Fragoso

  3. Stanford Bio-X, Stanford University, Stanford, CA, USA

    Luis S. Mille-Fragoso

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  1. Xiaowei Zhang
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  2. Luis S. Mille-Fragoso
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Correspondence to Xiaowei Zhang or Luis S. Mille-Fragoso.

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Competing interests

X.Z. and L.S.M.-F. are co-inventors on a US provisional patent application no. 63/399,400, relating sense-and-response of proteins, peptides and small molecules using ligand-induced dimerization activating RNA editing, filed by Stanford University.

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Zhang, X., Mille-Fragoso, L.S. Enabling RNA-compatible synthetic receptors through RNA editing. Nat Rev Mol Cell Biol 26, 581 (2025). https://doi.org/10.1038/s41580-025-00863-y

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  • DOI: https://doi.org/10.1038/s41580-025-00863-y

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