Enhancing cell-based therapies with synthetic gene circuits responsive to molecular stimuli


Date

2024-10

Publication Type

Review Article

ETH Bibliography

yes

Citations

Altmetric

Data

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.

Publication status

published

Editor

Book title

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 check_circle

Notes

Funding

785800 - Electrogenetics - Shaping Electrogenetic Interfaces for Closed-Loop Voltage-Controlled Gene Expression (EC)

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