Evidence map›Paper›PMID 34496151›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021

Genetically Encoded Protein Thermometer Enables Precise Electrothermal Control of Transgene Expression.

Bozhidar-Adrian Stefanov, Ana P Teixeira, Maysam Mansouri, Adrian Bertschi, Krzysztof Krawczyk, Ghislaine Charpin-El Hamri, Shuai Xue, Martin Fussenegger

Open access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

20 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Traceless Regulation of Genetic Circuitry.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Review
  5. Remote-controlled genetics: A new frontier in precision therapy.Clinical and translational medicine · 2025
    Article
  6. Article
  7. Genetics-Based Targeting Strategies for Precise Neuromodulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  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

8 authors at 3 institutions in 2 countries.

Bozhidar-Adrian StefanovETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.
Ana P TeixeiraETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.
Maysam MansouriETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.
Adrian BertschiETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.
Krzysztof KrawczykETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.
Ghislaine Charpin-El HamriDépartement Génie Biologique, Institut Universitaire de Technologie, Villeurbanne, Cedex, F-69622, France.
Shuai XueETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.
Martin FusseneggerETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.ORCID 0000-0001-8545-667X
ETH Zurich · CHInstituts Universitaires de Technologie · FRUniversity of Basel · CH

Funding

European Research Council 785800National Centre of Competence in ResearchSwiss National Science Foundation 27449.2 PFLS-LS
6 · The paper itself

Abstract

Body temperature is maintained at around 37 °C in humans, but may rise to 40 °C or more during high-grade fever, which occurs in most adults who are seriously ill. However, endogenous temperature sensors, such as ion channels and heat-shock promoters, are fully activated only at noxious temperatures above this range, making them unsuitable for medical applications. Here, a genetically encoded protein thermometer (human enhanced gene activation thermometer; HEAT) is designed that can trigger transgene expression in the range of 37-40 °C by linking a mutant coiled-coil temperature-responsive protein sensor to a synthetic transcription factor. To validate the construct, a HEAT-transgenic monoclonal human cell line, FeverSense, is generated and it is confirmed that it works as a fever sensor that can temperature- and exposure-time-dependently trigger reporter gene expression in vitro and in vivo. For translational proof of concept, microencapsulated designer cells stably expressing a HEAT-controlled insulin production cassette in a mouse model of type-1 diabetes are subcutaneously implanted and topical heating patches are used to apply heat corresponding to a warm sensation in humans. Insulin release is induced, restoring normoglycemia. Thus, HEAT appears to be suitable for practical electrothermal control of cell-based therapy, and may also have potential for next-generation treatment of fever-associated medical conditions.

Indexed as

Alkaline PhosphataseAnimalsCell LineDiabetes Mellitus, ExperimentalHumansInsulinMicePlasmidsPromoter Regions, GeneticTemperatureThermometersAlkaline PhosphataseInsulindiabetesgene regulationgene switchessynthetic biologytemperature

Identifiers

PMID34496151
PMCPMC8564464
OpenAlexW3197159601

What OpenQuestion holds

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LicenceCC BY
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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.