Regulating MOR-Fc Fusion Protein Production via mRNA

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Solution Overview

Problem

Current therapies lack effective methods to regulate the production of fusion proteins, such as mu opioid receptor-Fc (MOR-Fc), which are active in the absence of opioid ligands, posing challenges for therapeutic applications.

Innovation Solution

The development of recombinant plasmids (RPs) that encode for the production of mRNA sequences, specifically targeting the expression of MOR-Fc, which can be administered to increase the bioavailability of the target biomolecule within a subject.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional therapy methods are used, then opioid ligands are required to activate MOR, but this limits therapeutic applications where ligand-free activation is needed

Engineering Contradiction:
Improvetherapeutic application flexibilityVSAvoidgene expression regulation system
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent introduces an intermediary system consisting of a regulatory RNA molecule that acts as a mediator between the gene encoding MOR and the actual protein expression. This regulatory RNA can be designed to enhance or suppress MOR-Fc expression in response to specific conditions, providing flexible therapeutic control without requiring opioid ligands. The intermediary allows independent regulation of receptor availability separate from ligand presence.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs parameter changes by modifying gene expression levels through designed RNA molecules that respond to specific biological parameters (such as cellular conditions, disease states, or external triggers). By changing the expression parameters of MOR-Fc rather than using ligand binding, the system achieves versatile therapeutic applications with a controllable complexity profile.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If MOR is activated without opioid ligands, then therapeutic effects can be achieved, but control over activation timing and location becomes challenging

Engineering Contradiction:
Improvetherapeutic effect consistencyVSAvoidactivation control
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies preliminary action by pre-designing regulatory RNA molecules with specific sequences and structures that are engineered to respond to predetermined conditions. These regulatory elements are incorporated into the gene construct beforehand, so that when specific biological parameters are met, the MOR-Fc expression is automatically activated or suppressed. This provides reliable therapeutic effects with built-in control mechanisms that simplify operational management.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The regulatory RNA system incorporates feedback mechanisms where the expression of MOR-Fc is continuously monitored and adjusted based on cellular conditions, disease states, or external triggers. The designed RNA molecules can respond to changes in the biological environment and modulate gene expression accordingly, ensuring reliable therapeutic effects while maintaining ease of operation through automatic regulation.

Inventive Principle:
Principle #23Feedback

3Productivity

If gene expression is upregulated to increase MOR-Fc bioavailability, then therapeutic effects are enhanced, but potential off-target effects and safety concerns increase

Engineering Contradiction:
ImproveMOR-Fc production rateVSAvoidoff-target effects
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing regulatory RNA molecules with tissue-specific or cell-type-specific expression patterns. The regulatory elements are engineered to be active only in specific locations within the body, ensuring that MOR-Fc is upregulated precisely where needed. This localized control enhances productivity in target tissues while minimizing off-target effects and safety concerns in other organs or cell types.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The regulatory system employs partial action by modulating MOR-Fc expression to achieve optimal therapeutic levels rather than maximal expression. The designed RNA molecules can fine-tune gene expression to match the specific therapeutic requirements, avoiding excessive production that could lead to off-target effects while maintaining sufficient productivity for effective treatment.

Inventive Principle:
Principle #16Partial or excessive action

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 increased bioavailability of MOR-Fc achieved through this method allows for therapeutic effects similar to those experienced with opioid ligand presence, including euphoria, sedation, and analgesia, without the need for opioid ligands.

Implementation Method 1

compositions for regulating gene expression and, consequently, the production of fusion proteins

Methodology Applied
Scientific EffectGene expression:

Implementation Method 2

the sequences of mRNA may encode for translation of a target biomolecule

Methodology Applied
Scientific EffectTranscription:

Implementation Method 3

the sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule

Methodology Applied
Scientific EffectTranslation:

Data Source

PatentUS12264329B1Composition for regulating production of fusion proteins
Publication Date: 2025.04.01 WYVERN PHARMACEUTICALS INC

AI summary

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a mu opioid receptor-Fc (MOR-Fc) that may be biologically active in the absence of an opioid ligand.