Evidence map›Paper›PMID 25360681›Full record

ArticleACS synthetic biology2014

Systematic transfer of prokaryotic sensors and circuits to mammalian cells.

Brynne C Stanton, Velia Siciliano, Amar Ghodasara, Liliana Wroblewska, Kevin Clancy, Axel C Trefzer, Jonathan D Chesnut, Ron Weiss, Christopher A Voigt

Abstract read
In one paragraph

Article in ACS synthetic biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
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  8. Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Brynne C StantonSynthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Velia Siciliano
Amar Ghodasara
Liliana Wroblewska
Kevin Clancy
Axel C Trefzer
Jonathan D Chesnut
Ron Weiss
Christopher A Voigt
Massachusetts Institute of Technology · USThermo Fisher Scientific (United States) · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
MIT Center for Integrative Synthetic BiologyP50GM098792 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2013 to 2017
$11.0M
Genetic circuits for high-throughput, multi-sensory, live cell microRNA profR01CA173712 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2013 to 2017
$2.5M
Characterization of Gradient-Responsive Genetic Programs Using Light SensorsR01GM095765 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VOIGT, CHRISTOPHER A · 2011 to 2014
$1.2M
NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA173712NIGMS NIH HHS P50 GM098792NIGMS NIH HHS P50GM098792NIGMS NIH HHS R01 GM095765
6 · The paper itself

Abstract

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >10(5) members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics.

Indexed as

AnimalsCHO CellsCricetinaeCricetulusEscherichia coliEscherichia coli ProteinsGenes, BacterialGenetic EngineeringHEK293 CellsHumansPhloroglucinolPromoter Regions, GeneticSynthetic BiologyTransgenes2,4-diacetylphloroglucinolEscherichia coli ProteinsPhloroglucinolTetR(B) protein, E coli2,4-diacetylphloroglucinol (DAPG)eukaryoteinducible systemmammalian synthetic biologysystems biology

Identifiers

PMID25360681
PMCPMC4277766
OpenAlexW2047331819

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.