Codon-Optimized RDH12 Gene Delivery for Retinal Dystrophy Treatment
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Solution Overview
Problem
Current treatments for RDH12-associated retinal dystrophies such as Leber congenital amaurosis type 13 and Retinitis Pigmentosa 53 are primarily supportive and do not effectively halt or reverse the progression of blindness, highlighting a need for more effective therapeutic options.
Innovation Solution
Development of therapeutic compositions and methods involving codon-optimized cDNA sequences encoding functional RDH12 protein, delivered via viral vectors like AAV, to express the protein in photoreceptor cells, potentially using gene editing systems to correct mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current supportive treatments are used for RDH12-associated retinal dystrophies, then patients receive basic care and management, but the progression of blindness continues unchecked
Solution Approach 1:
The patent uses adeno-associated virus (AAV) vectors as intermediaries to deliver the RDH12 gene to photoreceptor cells. The viral vector acts as a mediator between the therapeutic gene and the target cells, enabling efficient gene transfer and expression that supportive care alone cannot achieve.
Solution Approach 2:
The patent employs codon-optimized versions of the RDH12 gene sequence to improve protein expression efficiency. By changing the nucleotide sequence while maintaining the same amino acid sequence, the patent optimizes translational parameters to enhance protein production and stability in photoreceptor cells.
2Reliability
If gene augmentation therapy is implemented, then functional RDH12 protein can be produced in photoreceptor cells, but delivery efficiency and protein stability remain challenges
Solution Approach 1:
The patent uses codon-optimized gene sequences to change the nucleotide parameters while maintaining the same protein sequence. This optimization improves translation efficiency and protein stability, addressing delivery and expression challenges without increasing system complexity.
Solution Approach 2:
The patent creates multiple copies of the RDH12 gene within the AAV vector system and uses self-complementary AAV designs that generate double-stranded DNA copies in the target cells. This copying strategy ensures sufficient gene dosage and prolonged expression without requiring complex delivery mechanisms.
3Stability of the object's composition
If native RDH12 gene sequences are used, then the natural protein sequence is preserved, but expression levels and protein stability are insufficient for therapeutic effect
Solution Approach 1:
The patent applies codon optimization to change the nucleotide sequence parameters of the RDH12 gene while maintaining the identical amino acid sequence. This parameter change in the DNA level improves transcription and translation efficiency, leading to higher protein expression levels and enhanced stability without altering the protein's natural structure or function.
Data Source
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AI summary
Codon optimized nucleic acid sequences for RDH12 are provided, as well as recombinant viral vectors, such as AAV, expression cassettes, proviral plasmids or other plasmids containing the codon optimized sequence for functional RDH12. Recombinant vectors are provided that express the codon optimized, functional RDH12. Compositions containing these codon optimized sequences are useful in methods for treating, retarding or halting certain blinding diseases resulting from the absence, deficiency or inappropriate expression of RDH12. Other compositions and methods are providing for correcting a non-functional, defective or inadequately expressed native RDH12.