ArticleSynthetic biology (Oxford, England)2020
Elucidation and refinement of synthetic receptor mechanisms.
Article in Synthetic biology (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Conversion of natural cytokine receptors into orthogonal synthetic biosensors.Nature chemical biology · 2025Article
- Advancements in DNA-Driven Precision Modulation of Cell Surface Receptor for Programmable Cellular Functions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Post-transcriptional modular synthetic receptors.Nature chemical biology · 2025Article
- A generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors.Nature communications · 2025Article
- Exploring structure-function relationships in engineered receptor performance using computational structure prediction.GEN biotechnology · 2025Article
- Post-Transcriptional Modular Synthetic Receptors.bioRxiv : the preprint server for biology · 2024Article
- Exploring structure-function relationships in engineered receptor performance using computational structure prediction.bioRxiv : the preprint server for biology · 2024Article
- Enhancing extracellular vesicle cargo loading and functional delivery by engineering protein-lipid interactions.Nature communications · 2024Article
- Building Synthetic Biosensors Using Red Blood Cell Proteins.ACS synthetic biology · 2024Article
- Programmable synthetic receptors: the next-generation of cell and gene therapies.Signal transduction and targeted therapy · 2024Review
- Enabling neighbour labelling: using synthetic biology to explore how cells influence their neighbours.Development (Cambridge, England) · 2024Review
- Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits.Synthetic and systems biotechnology · 2023Article
- Instructional materials that control cellular activity through synthetic Notch receptors.Biomaterials · 2023Article
- Engineered membrane receptors with customizable input and output functions.Trends in biotechnology · 2023Article
- The evolution of synthetic receptor systems.Nature chemical biology · 2022Review
- Design and development of engineered receptors for cell and tissue engineering.Current opinion in systems biology · 2021Article
- Control of mammalian cell-based devices with genetic programming.Current opinion in systems biology · 2021Article
- Model-guided design of mammalian genetic programs.Science advances · 2021Article
- Elucidation and refinement of synthetic receptor mechanisms.Synthetic biology (Oxford, England) · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Synthetic receptors are powerful tools for engineering mammalian cell-based devices. These biosensors enable cell-based therapies to perform complex tasks such as regulating therapeutic gene expression in response to sensing physiological cues. Although multiple synthetic receptor systems now exist, many aspects of receptor performance are poorly understood. In general, it would be useful to understand how receptor design choices influence performance characteristics. In this study, we examined the modular extracellular sensor architecture (MESA) and systematically evaluated previously unexamined design choices, yielding substantially improved receptors. A key finding that might extend to other receptor systems is that the choice of transmembrane domain (TMD) is important for generating high-performing receptors. To provide mechanistic insights, we adopted and employed a Förster resonance energy transfer-based assay to elucidate how TMDs affect receptor complex formation and connected these observations to functional performance. To build further insight into these phenomena, we developed a library of new MESA receptors that sense an expanded set of ligands. Based upon these explorations, we conclude that TMDs affect signaling primarily by modulating intracellular domain geometry. Finally, to guide the design of future receptors, we propose general principles for linking design choices to biophysical mechanisms and performance characteristics.
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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.