Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia.
Interfaculty Doctoral Study of Biomedicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
Nat Commun. 2024 Aug 27;15(1):7369. doi: 10.1038/s41467-024-51620-2.
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.
深层组织中的细胞远程调控仍然是一个重大挑战。由于其非侵入性和精确控制的特点，低强度脉冲超声为体内治疗提供了希望。本研究使用脉冲超声来控制哺乳动物细胞中的钙内流，并设计了一种对深部组织声刺激有响应的治疗性细胞装置，而无需过度表达钙通道或气穴。确定了脉冲超声参数以诱导 HEK293 细胞中的钙内流。此外，还对细胞进行了工程改造，使其表达一种设计的钙反应转录因子，控制所选治疗基因的表达，构成治疗性细胞装置。在小鼠体内进行了工程声基因系统的功能验证，其中植入的抗炎细胞因子产生装置可有效缓解急性结肠炎，表现为结肠形态和组织病理学得到改善。这种方法为在深层组织中精确、局部控制工程细胞提供了一种强大的工具，展示了其在靶向治疗中的应用潜力。
