Evidence map›Paper›PMID 30203050›Full record

ArticleNucleic acids research2018

Synthetic control systems for high performance gene expression in mammalian cells.

Gabriele Lillacci, Yaakov Benenson, Mustafa Khammash

Abstract read
In one paragraph

Article in Nucleic acids research, 2018. 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
–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

50 citing papers in PubMed.

  1. Article
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  11. Noise Reduction in Resource-Coupled Multi-Module Gene Circuits through Antithetic Feedback Control.Proceedings of the ... IEEE Conference on Decision & Control. IEEE Conference on Decision & Control · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024
    Review
  16. Article
  17. Article
  18. Article
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  20. 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

3 authors.

Gabriele LillacciDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
Yaakov BenensonDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
Mustafa KhammashDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tunable induction of gene expression is an essential tool in biology and biotechnology. In spite of that, current induction systems often exhibit unpredictable behavior and performance shortcomings, including high sensitivity to transactivator dosage and plasmid take-up variation, and excessive consumption of cellular resources. To mitigate these limitations, we introduce here a novel family of gene expression control systems of varying complexity with significantly enhanced performance. These include: (i) an incoherent feedforward circuit that exhibits output tunability and robustness to plasmid take-up variation; (ii) a negative feedback circuit that reduces burden and provides robustness to transactivator dosage variability; and (iii) a new hybrid circuit integrating negative feedback and incoherent feedforward that combines the benefits of both. As with endogenous circuits, the complexity of our genetic controllers is not gratuitous, but is the necessary outcome of more stringent performance requirements. We demonstrate the benefits of these controllers in two applications. In a culture of CHO cells for protein manufacturing, the circuits result in up to a 2.6-fold yield improvement over a standard system. In human-induced pluripotent stem cells they enable precisely regulated expression of an otherwise poorly tolerated gene of interest, resulting in a significant increase in the viability of the transfected cells.

Indexed as

Gene Expression RegulationGene Regulatory NetworksAnimalsBiotechnologyCells, CulturedCHO CellsCricetinaeCricetulusHumansInduced Pluripotent Stem CellsPlasmidsSynthetic BiologyTrans-ActivatorsTransfectionTrans-Activators

Identifiers

PMID30203050
PMCPMC6182142

What OpenQuestion holds

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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.