ArticleCommunications biology2020
Engineering of an enhanced synthetic Notch receptor by reducing ligand-independent activation.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- TRACR: an anterograde transneuronal tracing system for genetic access across synapses and longitudinal circuit analysis.bioRxiv : the preprint server for biology · 2026Article
- Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026Article
- Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.International journal of molecular sciences · 2026Review
- Evaluation of the Ligand-Independent Activation of a VHH-Based Anti-CD19 SynNotch Receptor by Dual-Luciferase Assay.Analytical science advances · 2025Article
- Evolution of split-protein technologies in virology: From mechanistic discovery and diagnostics to therapeutic promise.Journal of virus eradication · 2025Review
- Detection of extracellular amyloid beta aggregates by an Aducanumab-based synNotch receptor: an in vitro proof-of-concept study.Journal of translational medicine · 2025Article
- Innovative gene engineering strategies to address tumor antigen escape in cell therapy.Journal of translational medicine · 2025Review
- Post-transcriptional modular synthetic receptors.Nature chemical biology · 2025Article
- In Situ synNotch-Programmed Astrocytes Sense and Attenuate Neuronal Apoptosis.International journal of molecular sciences · 2025Article
- Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues.Nature communications · 2025Article
- CAR-T Cell Therapy: Managing Side Effects and Overcoming Challenges.Advanced biomedical research · 2025Review
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- Engineering an αCD206-synNotch Receptor: Insights into the Development of Novel Synthetic Receptors.ACS synthetic biology · 2024Article
- Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024Review
- Post-Transcriptional Modular Synthetic Receptors.bioRxiv : the preprint server for biology · 2024Article
- Organoids and organoid extracellular vesicles-based disease treatment strategies.Journal of nanobiotechnology · 2024Review
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Hydrophobic mismatch drives self-organization of designer proteins into synthetic membranes.Nature communications · 2024Article
- Augmenting the Antitumor Efficacy of Natural Killer Cells via SynNotch Receptor Engineering for Targeted IL-12 Secretion.Current issues in molecular biology · 2024Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling is highly conserved in most animals and plays critical roles during neurogenesis as well as embryonic development. Synthetic Notch-based systems, modeled from Notch receptors, have been developed to sense and respond to a specific extracellular signal. Recent advancement of synNotch has shown promise for future use in cellular engineering to treat cancers. However, synNotch from Morsut et al. (2016) has a high level of ligand-independent activation, which limits its application. Here we show that adding an intracellular hydrophobic sequence (QHGQLWF, named as RAM7) present in native Notch, significantly reduced ligand-independent activation. Our enhanced synthetic Notch receptor (esNotch) demonstrates up to a 14.6-fold reduction in ligand-independent activation, without affecting its antigen-induced activation efficiency. Our work improves a previously reported transmembrane receptor and provides a powerful tool to develop better transmembrane signaling transduction modules for further advancement of eukaryotic synthetic biology.
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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 Socratic graph.