This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: The deoxyribonucleic acid (DNA) of living organisms contains regulatory elements that control when, where and to what extent specific genes are turned on or off. They can be co-opted to create "gene switches" that hold significant potential for understanding gene expression and for therapeutic applications, particularly for the noninvasive treatment or management of genetic disorders.
In recent years, researchers have developed several gene switches that enable the remote control of gene expression in living organisms using stimuli such as drugs, light, heat, ultrasound and electrical signals. However, current versions are limited in offering precise control over the timing and duration of gene expression. Additionally, drug-based gene switches can have undesirable adverse effects, while some stimuli, such as light, can make penetrating deeper tissues challenging.
Addressing these limitations, a research team led by Prof. Jongpil Kim and doctoral student Yerim Hwang from the Institute for Stem Cells and Regenerative Medicine at Dongguk University in the Republic of Korea has developed a novel electromagnetic field (EMF)-responsive gene switch. "In previous studies, extremely low-frequency EMFs have been shown to modulate expression of specific genes involved in stress response, epigenetic remodeling and cellular signaling pathways.
Moreover, EMF is noninvasive, fully reversible and can precisely penetrate target tissues or areas of the body, making it highly attractive for remote control of gene switches," Kim explains. "In this study, we utilized the promoter of the Lgr4 gene to create a robust EMF-inducible gene switch, and demonstrated its applications in Alzheimer's disease (AD) modeling and reversing aging markers in mice." To identify EMF-responsive genes, the researchers performed single-cell RNA sequencing (scRNA-seq) on mouse brain tissue following exposure to an EMF of 2.0 millitesla at 60 hertz. The team found exclusive upregulation of Lgr4 expression.
Through a series of validation experiments, researchers found that the promoter of Lgr4 was well suited for constructing an EMF-inducible (Ei) gene switch, exhibiting precise activation with no detectable adverse effects during the study. To evaluate the system in living animals, the researchers linked the Ei element to a reporter that produces green fluorescent protein (GFP), allowing gene activity to be visualized. They then generated transgenic mice carrying this reporter.
Following EMF exposure, the mice showed strong GFP expression throughout the body, while targeted EMF exposure produced localized gene expression in specific organs. When EMF stimulation was discontinued, gene expression returned to baseline within 24 hours, demonstrating that the Ei gene switch is highly tunable, reversible and capable of precise remote control of gene expression. Using a genome-wide CRISPR-Cas9 knockout screen, the researchers identified cytochrome b5 type B (Cyb5b), a membrane-associated protein, as the biological sensor for EMF.
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