rAAV Gene Augmentation With Codon-Optimized Retinal cDNA
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Choroideremia and achromatopsia are retinal diseases characterized by photoreceptor degeneration and visual impairment, with existing treatments lacking effective gene therapy solutions.
Innovation Solution
Development of codon-optimized cDNA sequences for Rab Escort Protein-1 (REP-1) and cyclic nucleotide gated channel proteins (CNGA3 and CNGB3) packaged in recombinant adeno-associated virus (rAAV) vectors for targeted gene augmentation therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional gene therapy vectors are used for choroideremia treatment, then the delivery of REP-1 gene is achieved, but the protein expression level and functional recovery are insufficient
Solution Approach 1:
The patent applies codon optimization to the REP-1 cDNA sequence, changing the nucleotide sequence parameters to match human cell preferences for translation efficiency. This results in enhanced protein expression levels and improved functional recovery in retinal cells, directly resolving the contradiction between reliable gene delivery and sufficient protein production.
2Reliability
If standard gene therapy approaches are used for achromatopsia, then CNGA3 or CNGB3 gene delivery is achieved, but the visual function improvement is limited
Solution Approach 1:
The patent optimizes the codon sequences for CNGA3 and CNGB3 genes to enhance translation efficiency in human retinal cells. This parameter optimization leads to higher protein expression and improved photoreceptor functional recovery, thereby enhancing visual function improvement while maintaining safe delivery parameters.
3Productivity
If wild-type cDNA sequences are used for gene therapy, then the native gene function is restored, but the expression efficiency in human cells is suboptimal
Solution Approach 1:
The patent optimizes codon usage patterns in the cDNA sequences to match human cellular preferences, thereby maximizing translation efficiency. Simultaneously, the optimized sequences maintain the correct amino acid sequences and protein folding characteristics to ensure full protein functionality, resolving the contradiction between expression efficiency and functional reliability.
Data Source
Figure 1
Figure 2
Figure 2
AI summary
Compositions and methods are provided for treating ocular disorders in a subject are provided. In one aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGA3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGB3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding REP-1. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.