High-performance chemical- and light-inducible recombinases in mammalian cells and mice

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; Justin Letendre; Jacob Beal; Wilson W Wong

doi:10.1038/s41467-019-12800-7

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High-performance chemical- and light-inducible recombinases in mammalian cells and mice

Journal article

Open access

Peer reviewed

High-performance chemical- and light-inducible recombinases in mammalian cells and mice

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, …

Nature communications, Vol.10(1), pp.4845-10

10/24/2019

DOI: 10.1038/s41467-019-12800-7

PMCID: PMC6813296

PMID: 31649244

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https://doi.org/10.1038/s41467-019-12800-7View

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Abstract

Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

Animals

Cold Temperature

DNA - metabolism

DNA Nucleotidyltransferases

Gene Regulatory Networks

Genetic Engineering - methods

HEK293 Cells

Humans

Integrases

Light

Mice

Recombinases - genetics

Recombinases - metabolism

Details

Title: Subtitle: High-performance chemical- and light-inducible recombinases in mammalian cells and mice
Creators: Benjamin H Weinberg - Boston University
Jang Hwan Cho - Boston University
Yash Agarwal - Boston University
N T Hang Pham - Boston University
Leidy D Caraballo - Boston University
Maciej Walkosz - Boston University
Charina Ortega - Boston University
Micaela Trexler - Boston University
Nathan Tague - Boston University
Billy Law - Boston University
William K J Benman - Boston University
Justin Letendre - Boston University
Jacob Beal - RTX
Wilson W Wong - Boston University
Resource Type: Journal article
Publication Details: Nature communications, Vol.10(1), pp.4845-10
DOI: 10.1038/s41467-019-12800-7
PMID: 31649244
PMCID: PMC6813296
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: S10 RR024523 / NCRR NIH HHS R01 GM129011 / NIGMS NIH HHS 1DP2CA186574 / U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) DP2 CA186574 / NCI NIH HHS
Language: English
Date published: 10/24/2019
Academic Unit: Electrical and Computer Engineering
Record Identifier: 9984627197902771

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