Optimized SUMF1 Expression Cassettes for Multiple Sulfatase Deficiency

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Solution Overview

Problem

There are currently no specific treatments available for multiple sulfatase deficiency (MSD), a disorder caused by aberrant SUMF1 gene expression or activity, leading to severe neurologic and somatic symptoms that result in early childhood mortality.

Innovation Solution

Development of optimized SUMF1 genes, expression cassettes, and vectors that enhance SUMF1 expression in human cells, providing therapeutic benefits for treating disorders associated with SUMF1 expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If wild-type SUMF1 gene is used, then endogenous expression is maintained, but therapeutic benefit is insufficient for treating MSD

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidSUMF1 expression level

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by optimizing the SUMF1 gene sequence through codon optimization and adjusting expression control elements (promoters, enhancers). This modifies the genetic parameters to increase SUMF1 protein expression levels and activity, thereby providing sufficient therapeutic benefit for treating multiple sulfatase deficiency while maintaining compatibility with host cells.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If no specific treatment is available, then current management is supportive care only, but disease progression and mortality remain severe

Engineering Contradiction:

Improvedisease outcomeVSAvoidtreatment availability

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent implements preliminary action by developing and preparing optimized SUMF1 expression cassettes and viral vectors before clinical application. The genetic material is pre-optimized for maximum expression and therapeutic effect, enabling proactive treatment intervention that can alter disease progression and improve outcomes for patients with multiple sulfatase deficiency.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If optimized SUMF1 gene is introduced, then therapeutic expression is achieved, but gene delivery and integration complexity increases

Engineering Contradiction:

Improvetherapeutic expressionVSAvoidgene delivery system

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs an intermediary approach by utilizing viral vectors (such as adeno-associated viruses) as delivery vehicles to transport the optimized SUMF1 gene into target cells. These vectors serve as intermediaries that facilitate efficient gene delivery and integration while managing the complexity of the therapeutic system through well-characterized delivery mechanisms.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS12516301B2Optimized SUMF1 genes and expression cassettes and their use

Publication Date: 2026.01.06 THE UNIV OF NORTH CAROLINA AT CHAPEL HILL

AI summary

This invention relates to polynucleotides comprising optimized SUMF1 open reading frame (ORF) sequences, vectors comprising the same, and methods of using the same for deliver) of the ORF to a cell or a subject and to treat disorders associated with aberrant expression of a SUMF1 gene or aberrant activity of a SUMF1 gene product in the subject, such as SUMF1 disease.