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.

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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Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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The Extrinsic Apoptotic Pathway

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