sdAb Receptor Pairing Proteins for Selective Cytokine Signaling
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Solution Overview
Problem
The limited number of cytokine receptor pairings in nature restricts the scope of signaling-competent receptor pairs, limiting therapeutic applications and causing adverse effects when natural cytokines are used as therapeutics.
Innovation Solution
Development of single-domain antibody (sdAb) binding proteins that specifically bind to cytokine receptor subunits, facilitating multimerization and intracellular signaling, thereby activating desired cell types while minimizing unwanted signaling in other cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If natural cytokines are used as therapeutics to activate desired cell types, then therapeutic efficacy is improved, but adverse effects occur due to unwanted signaling in other cells
Solution Approach 1:
The patent uses engineered cytokine variants as intermediaries that selectively bind to specific receptor pairings. These engineered cytokines act as mediators between the therapeutic goal and the target cells, achieving desired activation while avoiding unwanted signaling through engineered specificity to particular receptor combinations rather than broad natural cytokine binding
Solution Approach 2:
The patent applies local quality by engineering cytokines with differential binding affinities to different receptor pairings. Each engineered cytokine variant is designed to preferentially bind to specific receptor combinations on particular cell types, creating localized and selective therapeutic effects while minimizing systemic adverse effects through tailored receptor specificity
2Device complexity
If the number of cytokine receptor pairings is limited to those driven by natural ligands, then system complexity is reduced, but the scope of signaling-competent receptor pairs is restricted
Solution Approach 1:
The patent achieves universality by creating engineered cytokine variants that can bind to multiple different receptor pairings. These engineered cytokines are designed with enhanced versatility to activate various signaling pathways through different receptor combinations, expanding the functional scope beyond natural cytokine limitations while maintaining a manageable system framework
Solution Approach 2:
The patent applies parameter changes by modifying cytokine molecular structures to alter binding characteristics. Through engineered amino acid substitutions and structural modifications, the cytokines gain new binding specificities and affinities for different receptor pairings, expanding signaling capabilities without proportionally increasing system complexity
3Adaptability or versatility
If cytokines act as multispecific ligands binding to multiple receptors, then signaling versatility is improved, but selectivity for specific target cells decreases
Solution Approach 1:
The patent applies dynamics by engineering cytokines with conditional binding behavior. The engineered cytokine variants are designed to dynamically interact with different receptor pairings based on cellular context, expressing versatility when appropriate receptor combinations are present while maintaining selectivity through context-dependent binding affinity modulation
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
The sdAb binding proteins enhance therapeutic efficacy by selectively activating target cells, reducing adverse effects, and providing novel signaling pathways for treating neoplastic diseases and infectious diseases.
Implementation Method 1
the binding protein causes the multimerization of IL12Rβ1 and IL12Rβ2 and the multimerization results in the association of intracellular domains of IL12Rβ1 and IL12Rβ2 and intraceullar signaling
Data Source
AI summary
Provided herein are receptor binding proteins that bind to either natural cytokine receptor pairs or non-natural cytokine receptor pairs to create signaling diversity beyond natural receptor pairings.