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通过阻断重组酶功能实现下一代合成记忆。

Next generation synthetic memory via intercepting recombinase function.

机构信息

Georgia Institute of Technology, School of Chemical and Biomolecular Engineering, Atlanta, GA, USA.

出版信息

Nat Commun. 2023 Aug 29;14(1):5255. doi: 10.1038/s41467-023-41043-w.

DOI:10.1038/s41467-023-41043-w
PMID:37644045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10465543/
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.

摘要

我们提出了一种技术,通过重新利用转录编程(即我们的决策技术)部分,来调节(拦截)翻译后重组酶的功能,从而在活体系统中实现人工合成记忆。我们表明,人工合成记忆的拦截可以通过定点删除来促进可编程的失活功能,通过定点反转来促进可编程的获得功能,以及通过嵌套布尔逻辑运算进行人工合成记忆操作。我们可以为单个重组酶扩展拦截人工合成记忆容量超过 5 倍,并且可以并行对多个位点进行重新配置。拦截人工合成记忆的速度比以前几代基于重组酶的记忆快约 10 倍。我们假设我们的下一代记忆技术更快的重组速度是由于重组酶功能的翻译后调控。这种人工合成记忆的迭代与通过转录编程进行决策是互补的 - 因此可用于开发用于各种应用的智能合成生物系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/7a9d9ed17847/41467_2023_41043_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/ba926c429c55/41467_2023_41043_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/e8eedc4c1ada/41467_2023_41043_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/99a2d7520270/41467_2023_41043_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/7f37f311c231/41467_2023_41043_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/fe4fed16f667/41467_2023_41043_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/b9c0b2cfb5ba/41467_2023_41043_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/24ad74abeea7/41467_2023_41043_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/7a9d9ed17847/41467_2023_41043_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/ba926c429c55/41467_2023_41043_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/e8eedc4c1ada/41467_2023_41043_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/99a2d7520270/41467_2023_41043_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/7f37f311c231/41467_2023_41043_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/fe4fed16f667/41467_2023_41043_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/b9c0b2cfb5ba/41467_2023_41043_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/24ad74abeea7/41467_2023_41043_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef8/10465543/7a9d9ed17847/41467_2023_41043_Fig8_HTML.jpg

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