Codon-Optimized FIG4 Genes for CMT4J Gene Therapy

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Solution Overview

Problem

Current treatments for Charcot-Marie-Tooth Neuropathy type 4 J (CMT4J) are limited to symptomatic palliative care, and there is a need for an effective treatment that targets the cause of the disease.

Innovation Solution

Development of codon-optimized FIG4 genes, expression cassettes, and vectors capable of providing therapeutic levels of FIG4 expression to treat disorders associated with FIG4 expression, such as CMT4J.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If codon-optimized FIG4 genes are used, then therapeutic levels of FIG4 expression are achieved, but the complexity of gene therapy development increases

Engineering Contradiction:

Improvetherapeutic levels of FIG4 expressionVSAvoidcomplexity of gene therapy development

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by optimizing the codon sequence of the FIG4 gene to improve translation efficiency and protein expression levels. The codon optimization process modifies nucleotide parameters while maintaining amino acid sequence, thereby achieving therapeutic levels of FIG4 expression in patient cells.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses expression cassettes and vectors that copy the optimized FIG4 gene into host cells. The expression cassette includes promoter elements, regulatory sequences, and the optimized FIG4 coding sequence, which are replicated and expressed within the cell to produce therapeutic amounts of FIG4 protein.

Inventive Principle:

Principle #26Copying

2Reliability

If FIG4 gene therapy is administered, then underlying cause of CMT4J is addressed, but manufacturing and delivery complexity increases

Engineering Contradiction:

Improveaddressing underlying cause of CMT4JVSAvoidmanufacturing and delivery complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the gene therapy system into distinct functional components: the optimized FIG4 coding sequence, regulatory elements (promoters, enhancers), vector backbone, and delivery mechanisms. This segmentation allows for modular manufacturing and independent optimization of each component, reducing overall complexity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs vectors (such as adeno-associated viruses or plasmids) as intermediary carriers to deliver the optimized FIG4 gene into target cells. These vectors serve as mediators that simplify the delivery process by providing a standardized platform for gene transfer, overcoming the complexity of direct gene administration.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If therapeutic FIG4 expression is achieved, then clinical outcomes improve, but cost and resource requirements increase

Engineering Contradiction:

Improveclinical outcomesVSAvoidcost and resource requirements

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent employs promoters and regulatory elements that enable self-regulated expression of the FIG4 gene. The expression system is designed to activate FIG4 production in response to cellular conditions, reducing the need for external monitoring and adjustment, thereby lowering resource requirements for maintaining therapeutic levels.

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS12270057B2Optimized FIG4 genes and expression cassettes and their use

Publication Date: 2025.04.08 THE UNIV OF NORTH CAROLINA AT CHAPEL HILL

AI summary

This invention relates to polynucleotides comprising optimized FIG. 4 open reading frame (ORF) sequences, vectors comprising the same, and methods of using the same for delivery of the ORF to a cell or a subject and to treat disorders associated with aberrant expression of a FIG. 4 gene or aberrant activity of a FIG. 4 gene product in the subject, such as CMT4J.