Chemically Induced Protein Dimerization for Cannabidiol Sensing

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Solution Overview

Problem

Existing chemically induced dimerization (CID) systems lack sensitivity and specificity for a given ligand, limiting their versatility in small molecule sensing and actuation applications.

Innovation Solution

Development of recombinant antibodies with specific CDR1, CDR2, and CDR3 combinations, and fusion proteins that dimerize in the presence of cannabidiol, utilizing a camelid-based universal scaffold with high sequence identity, enabling precise ligand binding and dimerization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing chemically induced dimerization systems are used, then the basic dimerization function is achieved, but the sensitivity and specificity for ligand binding are insufficient

Engineering Contradiction:

Improveligand binding sensitivity and specificityVSAvoiddimerization system performance

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The antibody molecule is segmented into functional regions: the scaffold provides structural stability while the CDRs (complementarity-determining regions) provide ligand binding specificity. This segmentation allows independent optimization of binding affinity and structural integrity, resolving the contradiction between sensitivity and system reliability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different regions of the antibody have different functional qualities: the scaffold region provides conserved structural properties for stability, while the CDR regions provide variable binding properties for ligand specificity. This local differentiation enables simultaneous achievement of high sensitivity and reliable dimerization.

Inventive Principle:

Principle #3Local quality

2Measurement precision

If recombinant antibodies with specific CDR combinations are designed, then ligand binding specificity is improved, but the complexity of protein design and manufacturing increases

Engineering Contradiction:

Improveligand binding specificityVSAvoidprotein design and manufacturing complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

A universal antibody scaffold sequence is used across all recombinant antibodies, providing a standardized structural framework. Only the CDR regions are varied to achieve different ligand specificities. This universality simplifies manufacturing protocols and reduces design complexity while maintaining high binding specificity through modular CDR customization.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Ease of manufacture

If a universal scaffold is used for all antibody variants, then manufacturing consistency is improved, but the ability to accommodate different ligand specificities is reduced

Engineering Contradiction:

Improvemanufacturing consistencyVSAvoidligand specificity accommodation

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The antibody is divided into a conserved scaffold segment and variable CDR segments. The scaffold maintains manufacturing consistency across all variants, while the CDR segments can be independently customized to accommodate different ligand specificities. This segmentation resolves the contradiction between manufacturing ease and adaptability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The scaffold region maintains uniform structural properties for consistent manufacturing, while the CDR regions exhibit local variability to accommodate different ligands. This local differentiation allows the universal scaffold to support multiple ligand specificities without compromising manufacturing consistency.

Inventive Principle:

Principle #3Local quality

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 recombinant antibodies and fusion proteins demonstrate enhanced sensitivity and specificity for cannabidiol, facilitating effective small molecule sensing and actuation, with applications in drug testing and point-of-care detection.

Implementation Method 1

recombinant antibodies, comprising a set of complementarity-determining regions (CDRs) selected from the group consisting of a CDR1, CDR2, and CDR3 combination

Methodology Applied

Scientific EffectAntibody-ligand binding:

Implementation Method 2

chemically induced dimerization (CID) systems, in which two proteins dimerize only in the presence of a small molecule ligand

Methodology Applied

Scientific EffectChemically induced dimerization:

Data Source

PatentUS12415869B2Chemically induced protein dimerization systems

Publication Date: 2025.09.16 UNIV OF WASHINGTON

AI summary

The disclosure provides polypeptides, fusion proteins, kits, dimers, nucleic acids, expression vectors, or host cells for use hi chemically induced dimerization systems, exemplified by a chemically induced dimerization system in which two recombinant antibodies dimerize only in the presence of cannabidiol.