Evidence map›Paper›PMID 39953326›Full record

ArticleNature biomedical engineering2025

Nitroglycerin-responsive gene switch for the on-demand production of therapeutic proteins.

Mohamed Mahameed, Shuai Xue, Benjamin Danuser, Ghislaine Charpin-El Hamri, Mingqi Xie, Martin Fussenegger

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Article
  6. 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

6 authors.

Mohamed Mahameed *Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Shuai Xue *Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2521-3833
Benjamin DanuserDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Ghislaine Charpin-El HamriDépartement Génie Biologique, Institut Universitaire de Technologie, Université Claude Bernard Lyon 1, Villeurbanne Cedex, France.
Mingqi XieWestlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.ORCID http://orcid.org/0000-0001-5657-532X
Martin FusseneggerDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. fussenegger@bsse.ethz.ch.ORCID http://orcid.org/0000-0001-8545-667X

Funding

EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ElectroGene 785800EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) EnlightEuropean Molecular Biology Organization (EMBO) FellowshipNational Natural Science Foundation of China (National Science Foundation of China) 32071429Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) NCCR Molecular Systems Engineering
6 · The paper itself

Abstract

Gene therapies and cell therapies require precise, reversible and patient-friendly control over the production of therapeutic proteins. Here we present a fully human nitric-oxide-responsive gene-regulation system for the on-demand and localized release of therapeutic proteins through clinically licensed nitroglycerin patches. Designed for simplicity and robust human compatibility, the system incorporates human mitochondrial aldehyde dehydrogenase for converting nitroglycerin into nitric oxide, which then activates soluble guanylate cyclase to produce cyclic guanosine monophosphate, followed by protein kinase G to amplify the signal and to trigger target gene expression. In a proof-of-concept study, human cells expressing the nitroglycerin-responsive system were encapsulated and implanted subcutaneously in obese mice with type 2 diabetes. Transdermal nitroglycerin patches applied over the implant enabled the controlled and reversible production of glucagon-like peptide-1 throughout the 35-day experimental period, effectively restoring blood glucose levels in these mice without affecting heart rate or blood pressure. The approach may facilitate the development of safe, convenient and responsive implantable devices for the sustained delivery of biopharmaceuticals for the management of chronic diseases.

Indexed as

NitroglycerinAldehyde Dehydrogenase, MitochondrialAnimalsCyclic GMPDiabetes Mellitus, Type 2Glucagon-Like Peptide 1HumansMaleMiceMice, ObeseNitric OxideAldehyde Dehydrogenase, MitochondrialCyclic GMPGlucagon-Like Peptide 1Nitric OxideNitroglycerin

Identifiers

PMID39953326
PMCPMC12270905

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.