Remote Control of Eukaryotic Gene Expression by a Modular Ultrasound-Responsive RNA Toolkit.

Area of Science:

• Molecular Biology
• Biotechnology
• Genetic Engineering

Background:

• Remote control of biological processes is a significant challenge in genetics.
• Current ultrasound-based gene regulation (sonogenetics) is limited by channel specificity and cell-type applicability.
• Existing sonogenetic systems primarily target gene transcription.

Purpose of the Study:

• To develop a versatile, modular toolkit for regulating gene expression using ultrasound.
• To enable remote control of protein translation via ultrasound-responsive RNA carriers.
• To expand sonogenetics applications across diverse eukaryotic systems.

Main Methods:

• Engineered ultrasound-responsive RNA carriers releasing small molecule modulators.
• Incorporation of riboswitches or aptazymes within mRNA structures for modulator response.
• Testing the toolkit's efficacy in various eukaryotic cells (yeast to mammalian).

Main Results:

• The toolkit successfully modulated gene expression across different eukaryotic cell types.
• Ultrasound stimulation triggered the release of modulators, controlling mRNA translation.
• Achieved up to six-fold downregulation of protein levels in response to ultrasound.

Conclusions:

• The RNA-based sonogenetic toolkit offers a versatile platform for ultrasound-mediated gene expression control.
• This system expands sonogenetics beyond transcription to translation regulation in eukaryotes.
• Potential for future applications in remote, on-demand control of protein function in specific tissues.