4.8 Article

Next generation synthetic memory via intercepting recombinase function

Journal

NATURE COMMUNICATIONS
Volume 14, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-023-41043-w

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This study presents a technology that uses repurposed parts of Transcriptional Programming to regulate recombinase function and facilitate synthetic memory in the living system. The interception synthetic memory allows programmable loss-of-function and gain-of-function, as well as nested Boolean logical operations. It offers a 5-fold increase in memory capacity compared to previous generations and is 10 times faster. This memory technology complements decision-making via Transcriptional Programming and can be used in developing intelligent synthetic biological systems.
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 reconfi-guration specificity for multiple sites in parallel. Interception synthetic memory is similar to 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.

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