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

Filip Ivanovski, Maja Meško, Tina Lebar, Marko Rupnik, Duško Lainšček, Miha Gradišek, Roman Jerala () and Mojca Benčina ()
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Filip Ivanovski: National Institute of Chemistry, Hajdrihova 19
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
Mojca Benčina: National Institute of Chemistry, Hajdrihova 19

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51620-2

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