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

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

doi:10.1016/j.cell.2026.03.029

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

Cell. 2026 Apr 14:S0092-8674(26)00330-2. doi: 10.1016/j.cell.2026.03.029. Online ahead of print.

Authors

Affiliations

¹ Institute for Stem Cells and Regenerative Medicine (ISR), Department of 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.

PMID: 41985457
DOI: 10.1016/j.cell.2026.03.029

Abstract

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.