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.