Evidence map›Paper›PMID 32001704›Full record

ArticleNature communications2020

Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming.

Krzysztof Krawczyk, Leo Scheller, Hyojin Kim, Martin Fussenegger

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024
    Review
  7. Protein Gas Vesicles ofACS nano · 2024
    Article
  8. Article
  9. Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Engineering synthetic phosphorylation signaling networks in human cells.bioRxiv : the preprint server for biology · 2023
    Article
  15. Article
  16. Article
  17. The evolution of synthetic receptor systems.Nature chemical biology · 2022
    Review
  18. Article
  19. Review
  20. Review
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 at 2 institutions in 1 country.

Krzysztof KrawczykDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.ORCID http://orcid.org/0000-0001-7896-7519
Leo SchellerDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.ORCID http://orcid.org/0000-0003-2490-4015
Hyojin KimDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Martin FusseneggerDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland. fussenegger@bsse.ethz.ch.ORCID http://orcid.org/0000-0001-8545-667X
ETH Zurich · CHUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rewiring cellular sensors to trigger non-natural responses is fundamental for therapeutic cell engineering. Current designs rely on engineered receptors that are limited to single inputs, and often suffer from high leakiness and low fold induction. Here, we present Generalized Engineered Activation Regulators (GEARs) that overcome these limitations by being pathway-specific rather than input-specific. GEARs consist of the MS2 bacteriophage coat protein fused to regulatory or transactivation domains, and work by rerouting activation of the NFAT, NFκB, MAPK or SMAD pathways to dCas9-directed gene expression from genomic loci. This system enables membrane depolarization-induced activation of insulin expression in β-mimetic cells and IL-12 expression in activated Jurkat cells, as well as IL-12 production in response to the immunomodulatory cytokines TGFβ and TNFα in HEK293T cells. Engineered cells with the ability to reinterpret the extracellular milieu have potential for applications in immunotherapy and in the treatment of metabolic diseases.

Indexed as

GenomeCalcium SignalingCellular ReprogrammingCRISPR-Associated Protein 9Genetic EngineeringHEK293 CellsHumansImmunomodulationInflammationInsulinInterleukin-12Jurkat CellsLymphocyte ActivationMembrane PotentialsSignal TransductionT-LymphocytesCRISPR-Associated Protein 9InsulinInterleukin-12

Identifiers

PMID32001704
PMCPMC6992713
OpenAlexW3003522620

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.