Molecular electromagnetic sensor may enable remote-controlled gene therapy
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.
Researchers at the Institute for Stem Cells and Regenerative Medicine at Dongguk University in South Korea have created a groundbreaking electromagnetic field (EMF)-responsive gene switch. This innovative technology could revolutionize gene therapy by enabling remote-controlled gene expression in living organisms using noninvasive, reversible EMFs.
The gene switch was developed by linking the promoter of the Lgr4 gene to a reporter that produces green fluorescent protein (GFP). When exposed to EMFs of 2.0 millitesla at 60 hertz, the Lgr4 promoter showed exclusive upregulation in mouse brain tissue. Researchers validated the gene switch's ability to precisely activate gene expression without adverse effects.
When EMF stimulation was discontinued, gene expression returned to baseline within 24 hours, demonstrating tunability and reversibility. Using a genome-wide CRISPR-Cas9 knockout screen, the team identified cytochrome b5 type B (Cyb5b) as a molecular sensor for EMFs. Cyb5b triggers rhythmic calcium influx oscillations in cells when exposed to EMFs, activating target genes.
The researchers demonstrated several applications of the EMF-inducible gene switch, including modeling Alzheimer's disease and reversing aging markers in mice. Cyclic EMF exposure improved aging-associated markers in aged and progeroid mice without adverse effects. Additionally, the gene switch controlled the expression of the Tph2 gene, restoring serotonin levels and reducing depression-like behaviors in mice.
This breakthrough could transform gene therapy from a single, irreversible dose into simple, real-time treatments that could be administered by physicians or incorporated into wearable devices. However, further validation and testing are required before this technology can be widely adopted.
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