Codon-Optimized SLC13A5 Expression Cassettes for Citrate Transporter Disorder
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for citrate transporter disorder, caused by SLC13A5 gene mutations, are inadequate in providing meaningful and long-term therapeutic benefits, particularly in managing seizures and other symptoms such as seizures, global developmental delay, and movement disorders.
Innovation Solution
Development of optimized SLC13A5 genes and expression cassettes that are codon-optimized for expression in human cells, delivered via vectors like AAV, to restore therapeutic levels of SLC13A5 expression, thereby addressing aberrant gene expression or activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional SLC13A5 gene delivery methods are used, then the gene can be delivered to cells, but therapeutic levels of expression are not achieved
Solution Approach 1:
The patent applies codon optimization to change the nucleotide sequence parameters of the SLC13A5 gene while maintaining the same amino acid sequence. This parameter change optimizes the gene for mammalian cell expression, directly resolving the contradiction by achieving therapeutic expression levels without changing the protein product.
Solution Approach 2:
The patent creates an optimized copy of the SLC13A5 gene with improved codon usage for mammalian cells. This copied version maintains the original protein-coding sequence but uses synonymous codons that are more efficiently translated in mammalian systems, thereby achieving reliable therapeutic expression.
2Duration of action of moving object
If existing treatment methods are used, then some symptom management is achieved, but long-term therapeutic benefits are not provided
Solution Approach 1:
The patent employs gene therapy to establish long-term, sustained expression of the SLC13A5 protein. By delivering the optimized gene that integrates into the patient's genome or maintains stable episomal expression, the treatment provides durable therapeutic benefits that extend far beyond the duration of conventional medications, directly addressing the limitation of short-term symptom management.
Data Source
Figure 1~2
Figure 3~4C
Figure 5A~5B
AI summary
This invention relates to polynucleotides comprising optimized SLC13A5 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 SLC13A5 gene or aberrant activity of a SLC13A5 gene product in the subject, such as citrate transporter disorder.