Chimeric STING Receptor for Cyclic Dinucleotide Screening
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for screening medicaments targeting cyclic dinucleotides are inefficient due to the need for cell membrane permeability procedures or liposome encapsulation to activate the STING receptor, limiting the range of compounds that can be screened and reducing screening efficiency.
Innovation Solution
A recombinant vector expressing a novel receptor subtype M of STING, which is located on the cell surface and can directly sense extracellular cyclic dinucleotides, allowing for the development of a simplified screening method that omits the need for additional reagents or liposome encapsulation, enabling the identification and detection of subtype M of STING and its agonists or inhibitors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell membrane permeability procedure or liposome encapsulation is used to activate STING receptor, then the medicament can contact the STING receptor on endoplasmic reticulum, but the screening efficiency is reduced and the range of screenable medicaments is limited
Solution Approach 1:
The patent introduces a chimeric receptor as an intermediary component that bridges the extracellular space and the STING signaling pathway. This chimeric receptor comprises an extracellular domain that can bind medicaments and an intracellular domain that activates STING, eliminating the need for membrane permeabilization or liposome encapsulation while maintaining reliable medicament-receptor interaction.
Solution Approach 2:
The chimeric receptor is constructed by segmenting and recombining different receptor components: an extracellular domain from one receptor and an intracellular signaling domain from STING. This segmentation allows the creation of a hybrid molecule that performs both ligand binding and signal transactivation functions, resolving the contradiction between reliable contact and screening efficiency.
2Reliability
If cell membrane permeability procedure is used, then extracellular cyclic dinucleotides can reach intracellular STING receptor, but additional reagents and complex procedures are required
Solution Approach 1:
The chimeric receptor serves as a mediator that translates extracellular medicament binding into intracellular STING activation without requiring membrane permeabilization reagents. This intermediary structure simplifies the screening procedure by eliminating complex preparatory steps while ensuring reliable receptor activation.
Solution Approach 2:
The chimeric receptor is designed to autonomously perform both ligand binding and signal transduction functions within the cell membrane structure, eliminating the need for external reagents or complex procedures to facilitate medicament delivery to the intracellular STING pathway.
3Reliability
If liposome encapsulation is used to deliver medicaments, then the medicaments can reach STING receptor, but the screening process becomes more complex and time-consuming
Solution Approach 1:
The chimeric receptor acts as a direct intermediary that receives medicaments from the extracellular environment and transmits activation signals to STING, eliminating the time-consuming liposome encapsulation and transfection steps while maintaining reliable medicament delivery and receptor activation.
Solution Approach 2:
The chimeric receptor is pre-positioned in the cell membrane with its binding domain exposed to the extracellular space, allowing medicaments to directly interact with the receptor without requiring preliminary encapsulation or delivery steps, thus significantly reducing screening time.
Data Source
AI summary
Disclosed herein is a recombinant vector being capable of expressing a novel receptor that senses exogenous cyclic dinucleotides (subtype M of STING) and meanwhile disclosed herein are a method and a kit for specifically identifying and detecting the expression of the said receptor. Further, provided herein are a medicament screening model and a kit for screening agonists or inhibitors targeting subtype M of the novel gene STING and the use thereof. Use of the screening model and the kit could simplify the screening procedure, enhance the screening efficiency and expand the range of the medicaments to be screened.