Two- and three-input TALE-based AND logic computation in embryonic stem cells

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Two- and three-input TALE-based AND logic computation in embryonic stem cells

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Title: Two- and three-input TALE-based AND logic computation in embryonic stem cells
Author: Lienert, Florian; Torella, Joseph P.; Chen, Jan-Hung; Norsworthy, Michael; Richardson, Ryan R.; Silver, Pamela A.

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Citation: Lienert, Florian, Joseph P. Torella, Jan-Hung Chen, Michael Norsworthy, Ryan R. Richardson, and Pamela A. Silver. 2013. “Two- and three-input TALE-based AND logic computation in embryonic stem cells.” Nucleic Acids Research 41 (21): 9967-9975. doi:10.1093/nar/gkt758. http://dx.doi.org/10.1093/nar/gkt758.
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Abstract: Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals.
Published Version: doi:10.1093/nar/gkt758
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834826/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878975
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