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Nucleic Acids Res. 2013 Sep;41(16):e156. doi: 10.1093/nar/gkt605. Epub 2013 Jul 11.

Rapid, modular and reliable construction of complex mammalian gene circuits.

Author information

1
Department of Biological Engineering, Massachusetts Institute of Technology, 40 Ames Street, Cambridge, MA 02142, USA, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 40 Ames Street, Cambridge, MA 02142, USA and INRIA Paris-Rocquencourt, Le Chesnay, 78153, France.

Abstract

We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonstrate construction of synthetic gene circuits of up to 64 kb in size comprising 11 transcription units and 33 basic parts. We show robust gene expression control of multiple transcription units by small molecule inducers in human cells with transient transfection and stable chromosomal integration of these circuits. This framework enables development of complex gene circuits for engineering mammalian cells with unprecedented speed, reliability and scalability and should have broad applicability in a variety of areas including mammalian cell fermentation, cell fate reprogramming and cell-based assays.

PMID:
23847100
PMCID:
PMC3763561
DOI:
10.1093/nar/gkt605
[Indexed for MEDLINE]
Free PMC Article
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