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Next generation synthetic memory via intercepting recombinase function

Andrew E. Short, Dowan Kim, Prasaad T. Milner and Corey J. Wilson (corey.wilson@chbe.gatech.edu)
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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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41043-w

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