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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Guye P,Li Y,Wroblewska L,Duportet X,Weiss R

doi

10.1093/nar/gkt605

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

e156

issue

16

eissn

0305-1048

issn

1362-4962

pii

gkt605

journal_volume

41

pub_type

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