Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells

Open access
Date
2016-08Type
- Journal Article
Citations
Cited 32 times in
Web of Science
Cited 34 times in
Scopus
ETH Bibliography
yes
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Abstract
One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000120665Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
ElsevierOrganisational unit
03860 - Benenson, Yaakov / Benenson, Yaakov
Funding
281490 - Synthetic regulatory circuits for programmable control of cell physiology (EC)
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Show all metadata
Citations
Cited 32 times in
Web of Science
Cited 34 times in
Scopus
ETH Bibliography
yes
Altmetrics