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Next generation synthetic memory via intercepting recombinase function

Author

Listed:
  • Andrew E. Short

    (School of Chemical and Biomolecular Engineering)

  • Dowan Kim

    (School of Chemical and Biomolecular Engineering)

  • Prasaad T. Milner

    (School of Chemical and Biomolecular Engineering)

  • Corey J. Wilson

    (School of Chemical and Biomolecular Engineering)

Abstract

Here we present a technology to facilitate synthetic memory in a living system via repurposing Transcriptional Programming (i.e., our decision-making technology) parts, to regulate (intercept) recombinase function post-translation. We show that interception synthetic memory can facilitate programmable loss-of-function via site-specific deletion, programmable gain-of-function by way of site-specific inversion, and synthetic memory operations with nested Boolean logical operations. We can expand interception synthetic memory capacity more than 5-fold for a single recombinase, with reconfiguration specificity for multiple sites in parallel. Interception synthetic memory is ~10-times faster than previous generations of recombinase-based memory. We posit that the faster recombination speed of our next-generation memory technology is due to the post-translational regulation of recombinase function. This iteration of synthetic memory is complementary to decision-making via Transcriptional Programming – thus can be used to develop intelligent synthetic biological systems for myriad applications.

Suggested Citation

  • Andrew E. Short & Dowan Kim & Prasaad T. Milner & Corey J. Wilson, 2023. "Next generation synthetic memory via intercepting recombinase function," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41043-w
    DOI: 10.1038/s41467-023-41043-w
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    References listed on IDEAS

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    1. Ronald E. Rondon & Thomas M. Groseclose & Andrew E. Short & Corey J. Wilson, 2019. "Transcriptional programming using engineered systems of transcription factors and genetic architectures," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Brian D. Huang & Thomas M. Groseclose & Corey J. Wilson, 2022. "Transcriptional programming in a Bacteroides consortium," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Benjamin H. Weinberg & Jang Hwan Cho & Yash Agarwal & N. T. Hang Pham & Leidy D. Caraballo & Maciej Walkosz & Charina Ortega & Micaela Trexler & Nathan Tague & Billy Law & William K. J. Benman & Justi, 2019. "High-performance chemical- and light-inducible recombinases in mammalian cells and mice," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    4. Thomas M. Groseclose & Ronald E. Rondon & Zachary D. Herde & Carlos A. Aldrete & Corey J. Wilson, 2020. "Engineered systems of inducible anti-repressors for the next generation of biological programming," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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    Cited by:

    1. Brian D. Huang & Dowan Kim & Yongjoon Yu & Corey J. Wilson, 2024. "Engineering intelligent chassis cells via recombinase-based MEMORY circuits," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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