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Ultrasound-mediated spatial and temporal control of engineered cells in vivo

Author

Listed:
  • Filip Ivanovski

    (National Institute of Chemistry, Hajdrihova 19
    University of Ljubljana, Vrazov trg 2)

  • Maja Meško

    (National Institute of Chemistry, Hajdrihova 19)

  • Tina Lebar

    (National Institute of Chemistry, Hajdrihova 19)

  • Marko Rupnik

    (National Institute of Chemistry, Hajdrihova 19)

  • Duško Lainšček

    (National Institute of Chemistry, Hajdrihova 19)

  • Miha Gradišek

    (University of Ljubljana, Tržaška c. 25)

  • Roman Jerala

    (National Institute of Chemistry, Hajdrihova 19
    Centre of Technology of Gene and Cell Therapy, Hajdrihova 19)

  • Mojca Benčina

    (National Institute of Chemistry, Hajdrihova 19
    Centre of Technology of Gene and Cell Therapy, Hajdrihova 19
    Kongresni trg 12, 1000)

Abstract

Remote regulation of cells in deep tissue remains a significant challenge. Low-intensity pulsed ultrasound offers promise for in vivo therapies due to its non-invasive nature and precise control. This study uses pulsed ultrasound to control calcium influx in mammalian cells and engineers a therapeutic cellular device responsive to acoustic stimulation in deep tissue without overexpressing calcium channels or gas vesicles. Pulsed ultrasound parameters are established to induce calcium influx in HEK293 cells. Additionally, cells are engineered to express a designed calcium-responsive transcription factor controlling the expression of a selected therapeutic gene, constituting a therapeutic cellular device. The engineered sonogenetic system’s functionality is demonstrated in vivo in mice, where an implanted anti-inflammatory cytokine-producing cellular device effectively alleviates acute colitis, as shown by improved colonic morphology and histopathology. This approach provides a powerful tool for precise, localized control of engineered cells in deep tissue, showcasing its potential for targeted therapeutic delivery.

Suggested Citation

  • Filip Ivanovski & Maja Meško & Tina Lebar & Marko Rupnik & Duško Lainšček & Miha Gradišek & Roman Jerala & Mojca Benčina, 2024. "Ultrasound-mediated spatial and temporal control of engineered cells in vivo," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51620-2
    DOI: 10.1038/s41467-024-51620-2
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