2. Academic Validation
  3. Ultrasound-mediated spatial and temporal control of engineered cells in vivo

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

  • Nat Commun. 2024 Aug 27;15(1):7369. doi: 10.1038/s41467-024-51620-2.
Filip Ivanovski # 1 2,  Maja Meško # 1,  Tina Lebar 1,  Marko Rupnik 1,  Duško Lainšček 1,  Miha Gradišek 3,  Roman Jerala 4 5,  Mojca Benčina 6 7 8
Affiliations

Affiliations

  • 1 Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia.
  • 2 Interfaculty Doctoral Study of Biomedicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
  • 3 Faculty of Electrical Engineering, University of Ljubljana, Tržaška c. 25, Ljubljana, Slovenia.
  • 4 Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia. [email protected].
  • 5 CTGCT, Centre of Technology of Gene and Cell Therapy, Hajdrihova 19, Ljubljana, Slovenia. [email protected].
  • 6 Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia. [email protected].
  • 7 CTGCT, Centre of Technology of Gene and Cell Therapy, Hajdrihova 19, Ljubljana, Slovenia. [email protected].
  • 8 University of Ljubljana, Kongresni trg 12, 1000, Ljubljana, Slovenia. [email protected].
  • # Contributed equally.
PMID: 39191796 DOI: 10.1038/s41467-024-51620-2
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.

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