ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Engineering a Rapid Insulin Release System Controlled By Oral Drug Administration.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- ERAD-level gene switches for on-demand protein secretion and rapidly controlled gene therapies.Nature communications · 2026Article
- Synthetic closed-loop gene circuit for phenylalanine regulation.Nucleic acids research · 2025Article
- Nitroglycerin-responsive gene switch for the on-demand production of therapeutic proteins.Nature biomedical engineering · 2025Article
- A mediator-free sonogenetic switch for therapeutic protein expression in mammalian cells.Nucleic acids research · 2025Article
- Aspirin-responsive gene switch regulating therapeutic protein expression.Nature communications · 2025Article
- Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024Article
- Review
- A Gene-Switch Platform Interfacing with Reactive Oxygen Species Enables Transcription Fine-Tuning by Soluble and Volatile Pharmacologics and Food Additives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Eukaryotic release factor 1 from Euplotes promotes frameshifting at premature stop codons in human cells.iScience · 2024Article
- Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Current Technologies for Managing Type 1 Diabetes Mellitus and Their Impact on Quality of Life-A Narrative Review.Life (Basel, Switzerland) · 2023Review
- Small molecule-inducible gene regulatory systems in mammalian cells: progress and design principles.Current opinion in biotechnology · 2022Review
- Engineering receptors in the secretory pathway for orthogonal signalling control.Nature communications · 2022Article
- Engineering a Rapid Insulin Release System Controlled By Oral Drug Administration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Rapid insulin release plays an essential role in maintaining blood-glucose homeostasis in mammalians. Patients diagnosed with type-I diabetes mellitus experience chronic and remarkably high blood-sugar levels, and require lifelong insulin injection therapy, so there is a need for more convenient and less invasive insulin delivery systems to increase patients' compliance and also to enhance their quality of life. Here, an endoplasmic-reticulum-localized split sec-tobacco etch virus protease (TEVp)-based rapamycin-actuated protein-induction device (RAPID) is engineered, which is composed of the rapamycin-inducible dimerization domains FK506 binding protein (FKBP) and FKBP-rapamycin binding protein fused with modified split sec-TEVp components. Insulin accumulation inside the endoplasmic reticulum (ER) is achieved through tagging its C-terminus with KDEL, an ER-retention signal, spaced by a TEVp cleavage site. In the presence of rapamycin, the split sec-TEVp-based RAPID components dimerize, regain their proteolytic activity, and remove the KDEL retention signal from insulin. This leads to rapid secretion of accumulated insulin from cells within few minutes. Using liver hydrodynamic transfection methodology, it is shown that RAPID quickly restores glucose homeostasis in type-1-diabetic (T1DM) mice treated with an oral dose of clinically licensed rapamycin. This rapid-release technology may become the foundation for other cell-based therapies requiring instantaneous biopharmaceutical availability.
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Registered trials
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.