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Ultrasound-dependent modular gene expression regulation system

Precise spatial and temporal regulation of cells remains a significant endeavour. Optogenetics has advanced this goal by enabling remote cell manipulation through genetically encoded light-sensitive proteins, allowing control of various cellular processes. However, light’s limited ability to penetrate deep into tissues restricts its non-invasive use in larger animals, driving interest in alternative methods like ultrasound, which penetrates tissue more effectively. By integrating synthetic gene circuits, we can link gene expression control to diverse stimuli—like small molecules, light, and, even more promisingly, ultrasound. These advancements offer exciting potential for gene therapy, cellular reprogramming, and cell-based therapies, providing fine-tuned control over both exogenous and endogenous gene expression.

The invention presents a novel system for precise control of cellular gene expression using ultrasound. It is based on a calcium-responsive synthetic circuit, leveraging the ability of ultrasound to trigger increase of cytosolic Ca2+ levels. With this non-invasive system we can achieve a spatio-temporal regulation of gene expression. Moreover, the split transcription factor system is highly modular, allowing multiplexing, and fast adaptation to different target genes or different transcriptional regulation modes.

Main advantages:

• Non-invasive control of gene expression using low-intensity ultrasound.

• Avoids harmful hyperthermia, ensuring safer applications.

• Spatio-temporal control allows for precise and conditional activation.

• Modular system allows for multiplexing of gene regulation and fast adaptation to different targets.

 

Developed by: Department of Synthetic Biology and Immunology 

Technology readiness level: TRL 3

Intellectual property: Patent pending

Cooperation opportunity: Joint development, licensing or sale of intellectual property

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