dc.contributor.author | Lienert, Florian | en_US |
dc.contributor.author | Torella, Joseph P. | en_US |
dc.contributor.author | Chen, Jan-Hung | en_US |
dc.contributor.author | Norsworthy, Michael | en_US |
dc.contributor.author | Richardson, Ryan R. | en_US |
dc.contributor.author | Silver, Pamela A. | en_US |
dc.date.accessioned | 2014-03-11T02:47:35Z | |
dc.date.issued | 2013 | en_US |
dc.identifier.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. | en |
dc.identifier.issn | 0305-1048 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878975 | |
dc.description.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. | en |
dc.language.iso | en_US | en |
dc.publisher | Oxford University Press | en |
dc.relation.isversionof | doi:10.1093/nar/gkt758 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834826/pdf/ | en |
dash.license | LAA | en_US |
dc.title | Two- and three-input TALE-based AND logic computation in embryonic stem cells | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nucleic Acids Research | en |
dash.depositing.author | Lienert, Florian | en_US |
dc.date.available | 2014-03-11T02:47:35Z | |
dc.identifier.doi | 10.1093/nar/gkt758 | * |
dash.contributor.affiliated | Chen, Jan-Hung | |
dash.contributor.affiliated | Norsworthy, Michael | |
dash.contributor.affiliated | Richardson, Ryan R. | |
dash.contributor.affiliated | Lienert, Florian | |
dash.contributor.affiliated | Torella, Joseph P. | |
dash.contributor.affiliated | Silver, Pamela | |