Evidence map›Paper›PMID 26883397›Full record

ArticleACS synthetic biology2016

Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells.

Christopher Ede, Ximin Chen, Meng-Yin Lin, Yvonne Y Chen

Abstract read
In one paragraph

Article in ACS synthetic biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
–field-weighted citation impact
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

60 citing papers in PubMed.

  1. Article
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  13. A Massively ParallelACS synthetic biology · 2024
    Article
  14. Article
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  16. Article
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  20. A molecular toolbox to study progesterone receptor signaling.Journal of mammary gland biology and neoplasia · 2023
    Article
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

4 authors.

Christopher EdeDepartment of Chemical and Biomolecular Engineering, University of California-Los Angeles , Los Angeles, California 90095, United States.
Ximin ChenDepartment of Chemical and Biomolecular Engineering, University of California-Los Angeles , Los Angeles, California 90095, United States.
Meng-Yin LinDepartment of Chemical and Biomolecular Engineering, University of California-Los Angeles , Los Angeles, California 90095, United States.
Yvonne Y ChenDepartment of Chemical and Biomolecular Engineering, University of California-Los Angeles , Los Angeles, California 90095, United States.

Funding

Engineering of computational receptors and gene circuits for T-cell immunotherapyDP5OD012133 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, YVONNE YU-HSUAN · 2012 to 2016
$1.7M
NIH HHS DP5 OD012133
6 · The paper itself

Abstract

Inducible transcription systems play a crucial role in a wide array of synthetic biology circuits. However, the majority of inducible promoters are constructed from a limited set of tried-and-true promoter parts, which are susceptible to common shortcomings such as high basal expression levels (i.e., leakiness). To expand the toolbox for regulated mammalian gene expression and facilitate the construction of mammalian genetic circuits with precise functionality, we quantitatively characterized a panel of eight core promoters, including sequences with mammalian, viral, and synthetic origins. We demonstrate that this selection of core promoters can provide a wide range of basal gene expression levels and achieve a gradient of fold-inductions spanning 2 orders of magnitude. Furthermore, commonly used parts such as minimal CMV and minimal SV40 promoters were shown to achieve robust gene expression upon induction, but also suffer from high levels of leakiness. In contrast, a synthetic promoter, YB_TATA, was shown to combine low basal expression with high transcription rate in the induced state to achieve significantly higher fold-induction ratios compared to all other promoters tested. These behaviors remain consistent when the promoters are coupled to different genetic outputs and different response elements, as well as across different host-cell types and DNA copy numbers. We apply this quantitative understanding of core promoter properties to the successful engineering of human T cells that respond to antigen stimulation via chimeric antigen receptor signaling specifically under hypoxic environments. Results presented in this study can facilitate the design and calibration of future mammalian synthetic biology systems capable of precisely programmed functionality.

Indexed as

AnimalsCalibrationGene DosageGene ExpressionHumansMammalsPromoter Regions, GeneticReceptors, AntigenSynthetic BiologyT-LymphocytesTranscription, GeneticReceptors, Antigenadoptive T-cell therapychimeric antigen receptorsmammalian inducible promotersmammalian synthetic biologytranscriptional control

Identifiers

PMID26883397
PMCPMC4874895

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Registered trials

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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.