Liver-Specific Wnt Signal Enhancing Molecules

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Solution Overview

Problem

There is a need for liver-specific Wnt signal enhancing molecules that can modulate Wnt signaling in a tissue-specific manner to treat and prevent various diseases and disorders without causing unwanted effects in other tissues.

Innovation Solution

The development of liver-specific Wnt signal enhancing molecules comprising a domain that binds to E3 ubiquitin ligases ZNRF3 or RNF43 and a liver-specific cell surface receptor binding domain, which selectively enhances Wnt signaling in the liver by mediating the internalization or sequestration of these ligases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If R-spondins are used to enhance Wnt signaling, then Wnt signaling is amplified, but the effect is not tissue-specific due to widespread expression of LGR4-6 and ZNRF3/RNF43 in various tissues

Engineering Contradiction:

ImproveWnt signaling enhancementVSAvoidtissue-specificity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by creating a bispecific molecule where one binding domain targets LGR4-6 and the other targets ZNRF3/RNF43, enabling selective Wnt signaling enhancement in specific tissues (e.g., liver) where both receptors are co-expressed, while avoiding off-target effects in tissues where only one receptor is present

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The bispecific molecule acts as an intermediary that simultaneously interacts with both LGR4-6 and ZNRF3/RNF43, bridging the gap between widespread receptor expression and the need for tissue-specific signaling enhancement by coordinating the binding of both receptor types in a single molecular complex

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If Wnt signaling is modulated systemically, then therapeutic effects are achieved, but unwanted effects occur in other tissues

Engineering Contradiction:

Improvetherapeutic effectVSAvoidunwanted effects in other tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The bisspecific molecule achieves local quality by requiring co-expression of both LGR4-6 and ZNRF3/RNF43 for activation, which is selectively true for liver tissue, thereby delivering therapeutic effects to the liver while minimizing systemic off-target effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The molecule is segmented into two distinct binding domains, each responsible for binding to a specific receptor (LGR4-6 or ZNRF3/RNF43), allowing independent optimization of binding characteristics and enabling selective activation only where both segments can simultaneously engage their targets

Inventive Principle:

Principle #1Segmentation

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

This approach effectively stabilizes Wnt receptors and enhances Wnt signaling in a liver-specific manner, providing a therapeutic means to treat and prevent liver diseases and disorders associated with reduced Wnt signaling.

Implementation Method 1

mediating liver-specific internalization or sequestration of the E3 ligases, ZNRF3/RNF43

Methodology Applied

Scientific EffectInternalization:

Implementation Method 2

stabilizing Wnt receptors and enhancing Wnt signaling

Methodology Applied

Scientific EffectSignal stabilization:

Data Source

PatentUS20250171509A1Liver-specific WNT signal enhancing molecules and uses thereof

Publication Date: 2025.05.29 SURROZEN OPERATING INC

AI summary

The present disclosure provides liver-specific Wnt signal enhancing molecules, and related methods of using these molecules to increase Wnt signaling in liver tissues and treat liver diseases and disorders.