Enhancing cell-based therapies with synthetic gene circuits responsive to molecular stimuli
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Author / Producer
Date
2024-10
Publication Type
Review Article
ETH Bibliography
yes
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Abstract
Synthetic biology aims to contribute to the development of next-generation patient-specific cell-based therapies for chronic diseases especially through the construction of sophisticated synthetic gene switches to enhance the safety and spatiotemporal controllability of engineered cells. Indeed, switches that sense and process specific cues, which may be either externally administered triggers or endogenous disease-associated molecules, have emerged as powerful tools for programming and fine-tuning therapeutic outputs. Living engineered cells, often referred to as designer cells, incorporating such switches are delivered to patients either as encapsulated cell implants or by infusion, as in the case of the clinically approved CAR-T cell therapies. Here, we review recent developments in synthetic gene switches responsive to molecular stimuli, spanning regulatory mechanisms acting at the transcriptional, translational, and posttranslational levels. We also discuss current challenges facing clinical translation of cell-based therapies employing these devices.
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Publication status
published
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Book title
Journal / series
Volume
121 (10)
Pages / Article No.
2987 - 3000
Publisher
Wiley
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
cell therapies; designer cells; genetic switches; mammalian cell engineering; synthetic biology
Organisational unit
03694 - Fussenegger, Martin / Fussenegger, Martin
Notes
Funding
785800 - Electrogenetics - Shaping Electrogenetic Interfaces for Closed-Loop Voltage-Controlled Gene Expression (EC)