Cell. 2026 Apr 14. pii: S0092-8674(26)00330-2. [Epub ahead of print]
Junyeop Kim,
Yerim Hwang,
Sumin Kim,
Daeyeol Kwon,
Jeonghyun Park,
Byounggook Cho,
Saemin An,
Soi Kang,
Yunkyung Kim,
Seonghun Kim,
Christopher J Lengner,
Soochan Kim,
Youngeun Kwon,
Jung-Suk Sung,
Jongpil Kim.
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.
Keywords: AD; Alzheimer’s disease; EMFs; aging; depressive disorder; electromagnetic fields; gene switch; in vivo partial reprogramming; rejuvenation