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Published on: March 24, 2023
A caspase-3-activated protein expression system for apoptosis visualization and apoptosis-pyroptosis conversion to
Wen-Jie Shu1, Chunxia He1, Zhe Ma1
1Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China.
Abstract:
Dysregulation of cell death is a hallmark of cancer, and overcoming tumor resistance to apoptosis-inducing therapies remains challenging. Inducing immunogenic cell death (ICD), such as pyroptosis, is promising but currently lacks tools for in vivo monitoring and control. Here, we developed a caspase-3-activated, genetically encoded protein expression system-a programmable synthetic biology platform activated by the key apoptotic protease caspase-3-for apoptosis detection. Configured to express fluorescent or luciferase proteins, it enabled high-resolution live-cell apoptosis imaging and in vivo tumor bioluminescence imaging, and it served as a screening tool for proapoptotic microRNAs. Most importantly, engineering it to express a pyroptosis effector triggered apoptosis-coupled pyroptosis, achieving potent cancer cell killing and enhanced in vivo antitumor efficacy. This versatile platform advances apoptosis detection and its conversion to potent ICD, offering an adaptable approach for cancer theranostics.
Insights
Researchers developed a synthetic biology platform to detect apoptosis (programmed cell death) and trigger immunogenic cell death (ICD) in cancer. This tool enhances cancer theranostics by enabling in vivo monitoring and potent cell killing.
Area of Science:
- Synthetic biology
- Cancer biology
- Immunogenic cell death
Background:
- Dysregulated cell death is a key feature of cancer, posing challenges for apoptosis-inducing therapies.
- Current methods for monitoring and controlling in vivo immunogenic cell death (ICD), like pyroptosis, are limited.
Purpose of the Study:
- To develop a programmable synthetic biology platform for apoptosis detection and conversion to ICD.
- To enable in vivo monitoring and control of cancer cell death pathways.
Main Methods:
- Engineered a caspase-3-activated, genetically encoded protein expression system.
- Utilized the system for live-cell apoptosis imaging and in vivo tumor bioluminescence imaging.
- Employed the platform as a screening tool for proapoptotic microRNAs and engineered it to trigger pyroptosis.
Main Results:
- The system enabled high-resolution apoptosis imaging and in vivo tumor monitoring.
- Successfully screened proapoptotic microRNAs using the platform.
- Engineering the system to express a pyroptosis effector resulted in apoptosis-coupled pyroptosis, potent cancer cell killing, and enhanced in vivo antitumor efficacy.
Conclusions:
- The developed platform provides a versatile tool for apoptosis detection and its conversion to potent ICD.
- This approach offers an adaptable strategy for cancer theranostics, advancing monitoring and therapeutic interventions.
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