Source 1primary paper2025MED
Toolkit/CiGSDME
CiGSDME
Also known as: chemically inducible GSDME platform
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The source describes a chemically inducible gene circuit that harnesses GSDME to trigger pyroptotic cell death on demand; the upstream web research summary states that the engineered platform is explicitly named CiGSDME.
Usefulness & Problems
No literature-backed usefulness or problem-fit explainer has been materialized for this record yet.
Published Workflows
Objective: Engineer and functionally validate a chemically inducible GSDME-based gene circuit for precise, externally controlled tumor-cell killing in colorectal cancer models.
Why it works: The workflow rewires GSDME so activation depends on an engineered protease recognition sequence, then couples that trigger to inducible protease variants controlled by an approved small molecule, allowing external timing of pyroptosis before testing antitumor effects in organoids and xenografts.
GSDME cleavagepore formationpyroptotic cell lysisprotease-site rewiringsmall-molecule inducible protease engineeringorganoid validationxenograft validation
Stages
- 1.Design of rewired inducible pyroptosis circuit(library_design)
This stage creates a GSDME effector that can be activated on demand by an engineered, drug-regulated protease rather than by its native proteolytic trigger.
Selection: Replace the native GSDME activation motif with a customized protease recognition sequence and pair it with inducible protease variants regulated by a small molecule.
- 2.Organoid functional characterization(functional_characterization)
This stage tests whether the engineered control logic produces the intended pyroptotic mechanism in a disease-relevant ex vivo model before in vivo testing.
Selection: Assess whether inducer administration produces rapid GSDME cleavage, pore formation, and cell lysis in patient-derived organoids.
- 3.Xenograft confirmatory validation(in_vivo_validation)
This stage evaluates whether externally controlled pyroptosis can translate into tumor growth inhibition in vivo using oral drug administration.
Selection: Test whether oral treatment with the approved drug suppresses tumor growth in a xenograft model.
Steps
- 1.Replace native GSDME activation motif with a customized protease recognition sequenceengineered effector construct
Rewire GSDME so its activation can be controlled by a chosen protease input.
The effector must first be made responsive to an orthogonal protease before small-molecule control can be imposed through inducible protease variants.
- 2.Engineer small-molecule-regulated inducible protease variantscontrol module
Create a drug-gated trigger that activates the rewired GSDME construct on demand.
After rewiring the GSDME cleavage site, a matching inducible protease is needed to provide external temporal control using the approved small molecule.
- 3.Administer inducer in patient-derived organoid models and assess pyroptosis outputsengineered system under test
Determine whether the inducible circuit produces the intended mechanistic outputs of pyroptosis in a disease-relevant model.
Organoid testing provides functional evidence of GSDME cleavage, pore formation, and cell lysis before moving to in vivo tumor studies.
- 4.Treat xenograft-bearing animals orally with the approved drug and measure tumor growth responseengineered system under in vivo validation
Test whether oral drug induction of the circuit yields tumor suppression in vivo.
In vivo validation follows organoid mechanistic success to determine whether the externally controlled pyroptosis strategy translates into tumor growth inhibition.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
Photocleavageproteolytic cleavagepyroptotic pore formationsmall-molecule inducible switchingTechniques
Computational DesignTarget processes
No target processes tagged yet.
Input: Chemical
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
In patient-derived organoid models, inducer administration caused rapid GSDME cleavage, pore formation, and robust cell lysis.
In patient-derived organoid models, administration of the inducer led to rapid GSDME cleavage, pore formation, and robust cell lysis.
Engineering inducible protease variants regulated by an orally bioavailable, clinically approved small molecule enabled precise temporal control of pyroptosis.
By engineering inducible protease variants whose activity is tightly regulated by an orally bioavailable, clinically approved small molecule, we achieved precise temporal control of pyroptosis.
In a xenograft model, oral treatment with the approved drug led to marked tumor growth inhibition.
In a xenograft model, oral treatment with the approved drug led to marked tumor growth inhibition.
The platform rewires GSDME activation by replacing its native proteolytic activation motif with a customized protease recognition sequence.
We substituted its native proteolytic activation motif with a customized protease recognition sequence.
The paper reports a chemically inducible gene circuit that uses GSDME to trigger pyroptotic cell death on demand.
Here, we report the design and functional validation of a chemically inducible gene circuit that harnesses Gasdermin E (GSDME) to trigger pyroptotic cell death on demand.
The strategy uses the safety and pharmacokinetics of an approved drug to enable programmable cell death for targeted elimination of treatment-resistant tumors.
This strategy utilizes the safety and pharmacokinetics of an approved drug to enable programmable cell death, providing a versatile platform for the targeted elimination of treatment-resistant tumors.
Approval Evidence
1 source6 linked approval claimsfirst-pass slug cigsdme
The source describes a chemically inducible gene circuit that harnesses GSDME to trigger pyroptotic cell death on demand; the upstream web research summary states that the engineered platform is explicitly named CiGSDME.
Source:
application resultsupports
In patient-derived organoid models, inducer administration caused rapid GSDME cleavage, pore formation, and robust cell lysis.
In patient-derived organoid models, administration of the inducer led to rapid GSDME cleavage, pore formation, and robust cell lysis.
Source:
control mechanismsupports
Engineering inducible protease variants regulated by an orally bioavailable, clinically approved small molecule enabled precise temporal control of pyroptosis.
By engineering inducible protease variants whose activity is tightly regulated by an orally bioavailable, clinically approved small molecule, we achieved precise temporal control of pyroptosis.
Source:
in vivo resultsupports
In a xenograft model, oral treatment with the approved drug led to marked tumor growth inhibition.
In a xenograft model, oral treatment with the approved drug led to marked tumor growth inhibition.
Source:
mechanism designsupports
The platform rewires GSDME activation by replacing its native proteolytic activation motif with a customized protease recognition sequence.
We substituted its native proteolytic activation motif with a customized protease recognition sequence.
Source:
tool designsupports
The paper reports a chemically inducible gene circuit that uses GSDME to trigger pyroptotic cell death on demand.
Here, we report the design and functional validation of a chemically inducible gene circuit that harnesses Gasdermin E (GSDME) to trigger pyroptotic cell death on demand.
Source:
translational rationalesupports
The strategy uses the safety and pharmacokinetics of an approved drug to enable programmable cell death for targeted elimination of treatment-resistant tumors.
This strategy utilizes the safety and pharmacokinetics of an approved drug to enable programmable cell death, providing a versatile platform for the targeted elimination of treatment-resistant tumors.
Source:
Comparisons
No literature-backed comparison notes have been materialized for this record yet.
Ranked Citations
- 1.