Synthetic IL-23 Biosensors for Precise Gene Expression Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing technologies face challenges in precisely controlling gene expression and sensing external cues for customized receptor assembly, particularly for targeting IL-23, which is crucial in treating inflammatory diseases and cancer.
Innovation Solution
Development of synthetic IL-23 biosensors using the Modular Extracellular Sensor Architecture (MESA) that combine IL-23 extracellular ligand-binding domains with transmembrane and intracellular dimerizing domains, enabling proteolytic release of a transcription factor upon receptor dimerization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If natural receptors are used to sense IL-23, then the system can detect the cytokine, but the signaling pathway interferes with native cellular processes and lacks precision in controlling gene expression
Solution Approach 1:
The receptor system is divided into separate modular components: an extracellular IL-23 binding domain, a transmembrane domain, and an intracellular signaling domain. This segmentation allows each component to be independently optimized and assembled, enabling precise control over gene expression while simplifying the overall system architecture by eliminating complex native signaling pathways.
Solution Approach 2:
A synthetic intermediary signaling pathway is introduced that acts as a mediator between IL-23 detection and gene expression control. This intermediary system uses engineered transcription factors and promoter elements to translate receptor activation into precise gene expression outcomes, decoupling the sensing function from the native complex signaling cascade.
2Adaptability or versatility
If customized receptor assembly is attempted for IL-23 targeting, then selective sensing can be achieved, but assembling functional receptors with precise control remains challenging
Solution Approach 1:
The patent creates a universal receptor platform where standardized modular components can be interchangeably assembled to target different cytokines or achieve different signaling outcomes. The conserved transmembrane and intracellular domains serve as universal building blocks that can be paired with various extracellular binding domains, simplifying the assembly process while maintaining adaptability for customized IL-23 sensing applications.
3Measurement precision
If existing biosensor systems are used, then general sensing capability is provided, but high-selectivity sensing of IL-23 with targeted therapeutic response is not achieved
Solution Approach 1:
The extracellular domain of the receptor is specifically engineered with high-affinity IL-23 binding characteristics while the intracellular domain is optimized for reliable signal transduction. This local quality differentiation ensures that the receptor maintains high selectivity for IL-23 at the binding site while simultaneously providing reliable and consistent therapeutic response through the signaling domain, resolving the contradiction between selectivity and reliability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables high-selectivity sensing of IL-23, facilitating targeted therapeutic responses and diagnostics, and providing tools for studying disease pathology.
Implementation Method 1
the intracellular dimerizing domain of the first protein comprises, consists of, or consists essentially of a first half of a split protease. In some other aspects, the intracellular dimerizing domain of the second protein comprises, consists of, or consists essentially of (i) a complementary second half of the split protease, (ii) a protease cleavage site (PCS), and (iii) a transcription factor linked thereto. In some embodiments, the split protease components reconstitute upon dimerization of the first protein and the second protein, cleaving the PCS and releasing the transcription factor.
Data Source
AI summary
The present disclosure relates generally to the field of synthetic receptors and their uses. More specifically, the present disclosure relates novel synthetic receptors that target IL-23 and the use of such receptor in the treatment of conditions involving immune dysfunction, particularly autoimmunity.