Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression

# Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression *Published: 2026 Apr 14* Chemistry, Dongguk University, Seoul 04620, Republic of Korea. (2)Department of Biomedical Sciences, School of Veterinary Medicine and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. (3)School of Electronic and Electrical Engineering, Institute of IT Convergence, Hankyong National University, Anseong, Republic of Korea. (4)Department of Biomedical Engineering, Dongguk University, Ilsan 10326, Republic of Korea. (5)Department of Life Science, Dongguk University, Seoul 10326, Gyeonggi-do, Republic of Korea. (6)Institute for Stem Cells and Regenerative Medicine (ISR), Department of Chemistry, Dongguk University, Seoul 04620, Republic of Korea. Electronic address: jpkim153@dongguk.edu. Gaining precise control of gene expression is crucial in biomedical applications. However, spatiotemporal precision remains challenging. Here, we present a remotely controlled in vivo gene switch responsive to electromagnetic fields (EMFs) that enables precise spatiotemporal activation of target genes. We uncovered the EMF-inducible gene switch activation mechanism via a CRISPR-Cas9 screen, identifying cytochrome b5 type B (Cyb5b) as an essential mediator likely acting as an EMF sensor. The EMF-inducible gene switch was activated by rhythmic oscillatory calcium dynamics rather than generic calcium influx, defining a precisely tuned and bio-orthogonal induction mechanism. Functionally, EMF activation of the Oct4-Sox2-Klf4 (OSK) cassette induced in vivo partial reprogramming in aged mice, conditional expression of human mutant amyloid precursor protein (APP) for Alzheimer's disease (AD) modeling recapitulated pathological features, and EMF-mediated Tph2 expression restored serotonergic activity and ameliorated depressive-like behaviors in Tph2-mutant depression mice. Overall, a remotely controlled EMF-inducible gene switch represents a versatile and effective biomedical platform. DOI: 10.1016/j.cell.2026.03.029