Despite remarkable progress in synthetic biology and cell engineering, current cell therapy technologies still face notable limitations. Existing gene switches mainly rely on transcriptional or translational regulation to control vesicle release, leading to response delays of several hours or even days. Such delays are often inadequate for applications that require immediate or precisely timed responses.

To address this challenge, our team developed a signal-regulated rapid vesicle release system at the post-translational level. Using mammalian cells as the foundation, we integrated multiple types of trigger signals, including light and small molecules, to construct a platform capable of rapid, signal-induced vesicle secretion. This system fundamentally overcomes the slow response cycle inherent in transcriptional and translational regulation, enabling fast, reversible responses to external stimuli while maintaining excellent compatibility and stability in mammalian cells. Through protein engineering and vesicle modification, we also ensured the specificity and safety of the released substances.

This technology not only provides a new tool for advancing cell therapy, but also has broad potential in fields such as disease monitoring, cell signaling research, and biomanufacturing, offering new strategies to meet biomedical and industrial needs. On this page, we outline our implementation strategy, the societal impact of our project, and the connection between our design objectives and real-world applications. We also identify potential user groups and highlight the importance of responsible, ethical utilization.

The core users of our system include the medical, research, and biotechnology communities that require precise and programmable control of cell functions. The most promising application areas are cell therapy and cell-based monitoring.

In cell therapy, autologous cells can be engineered to respond to specific stimulation signals and release therapeutic proteins, such as hormones or drugs, in a controllable manner. Clinicians could regulate vesicle release in real time based on patient conditions to treat secretory disorders. Moreover, cells designed to sense internal physiological cues could autonomously adjust secretion to maintain homeostasis. For example, in type 1 diabetes, increased blood glucose leads to calcium influx in pancreatic β cells. By engineering β cells to link calcium-responsive signaling with the SPARK system, insulin release could be rapidly and proportionally triggered by rising blood glucose. Encapsulation of these modified cells in biocompatible microcapsules would allow fast, on-demand insulin secretion after transplantation, potentially reducing or eliminating the need for external insulin injections.

In cell monitoring, engineered cells can be designed to sense disease-related factors or biomarkers. When exposed to patient samples such as blood or urine, these reporter cells would release detectable proteins upon stimulation, enabling rapid and convenient disease screening. Measuring secreted reporter levels could quickly indicate the presence or severity of disease, supporting early diagnosis and high-throughput testing.

Beyond therapeutic and diagnostic applications, this technology could serve as a universal functional switch for laboratories working on gene therapy, signaling pathways, or metabolic engineering. In industrial biotechnology, SPARK can act as a metabolic switch to dynamically regulate production lines, improving protein yield and reducing manufacturing costs. In agriculture, similar principles could be applied to optimize cellular functions in crops and livestock, enhancing productivity and environmental adaptability.

Figure 1.Applications of SPARK in Cell Therapy and Cell Monitoring

To ensure feasibility and robustness, we plan to iteratively optimize the response speed, regulatory specificity, and cross-cell compatibility of the SPARK system, guided by feedback from synthetic biology research and iGEM community evaluation. Parallel efforts will focus on intellectual property protection to safeguard innovation and promote responsible use.

Implementation will proceed in stages. Initial validation will involve testing core functions in model mammalian cell lines. Subsequent application-specific studies will refine parameters and ensure compliance with relevant regulations, including medical ethics, industrial biosafety, and agricultural standards. After verification, scenario-specific solutions will be developed and communicated to potential users.

During development, challenges such as adapting the system across diverse cellular contexts and maintaining robustness under complex signal environments are anticipated. These challenges will drive further optimization through iterative design, ensuring that SPARK remains a flexible, stable, and scalable platform capable of supporting a wide range of biomedical and industrial applications.