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

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.

AI evidence extraction

Main findings

The study reports an in vivo EMF-responsive gene switch for remote spatiotemporal control of gene expression in mice. A CRISPR-Cas9 screen identified Cyb5b as an essential mediator, and the switch was activated by rhythmic oscillatory calcium dynamics; EMF-triggered expression enabled partial reprogramming, AD-related APP expression with pathological features, and Tph2 expression that improved depressive-like behaviors in a mouse model.

Outcomes measured

• EMF-inducible gene switch activation
• Rhythmic oscillatory calcium dynamics
• In vivo partial reprogramming via OSK cassette
• Conditional expression of human mutant APP for Alzheimer's disease modeling
• Pathological features in AD model
• Tph2 expression
• Serotonergic activity
• Depressive-like behaviors

Limitations

• Exposure parameters were not specified in the abstract
• Sample size was not reported in the abstract
• Findings are from animal models and may not generalize to humans

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    "exposure": {
        "band": "unknown",
        "source": "other",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": "Aged mice and mouse disease models, including Tph2-mutant depression mice",
    "sample_size": null,
    "outcomes": [
        "EMF-inducible gene switch activation",
        "Rhythmic oscillatory calcium dynamics",
        "In vivo partial reprogramming via OSK cassette",
        "Conditional expression of human mutant APP for Alzheimer's disease modeling",
        "Pathological features in AD model",
        "Tph2 expression",
        "Serotonergic activity",
        "Depressive-like behaviors"
    ],
    "main_findings": "The study reports an in vivo EMF-responsive gene switch for remote spatiotemporal control of gene expression in mice. A CRISPR-Cas9 screen identified Cyb5b as an essential mediator, and the switch was activated by rhythmic oscillatory calcium dynamics; EMF-triggered expression enabled partial reprogramming, AD-related APP expression with pathological features, and Tph2 expression that improved depressive-like behaviors in a mouse model.",
    "effect_direction": "benefit",
    "limitations": [
        "Exposure parameters were not specified in the abstract",
        "Sample size was not reported in the abstract",
        "Findings are from animal models and may not generalize to humans"
    ],
    "evidence_strength": "low",
    "confidence": 0.89000000000000001332267629550187848508358001708984375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "EMF-inducible gene switch",
        "gene expression control",
        "animal study",
        "mouse model",
        "Cyb5b",
        "calcium oscillations",
        "partial reprogramming",
        "OSK",
        "Alzheimer's disease model",
        "Tph2",
        "depressive-like behavior"
    ],
    "suggested_hubs": []
}

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