Gene Modulators for Retinal Degeneration via Nuclear Hormone Receptors
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Solution Overview
Problem
Current treatments lack effective solutions for ocular diseases characterized by retinal degeneration, such as enhanced S-cone syndrome and retinitis pigmentosa, which are associated with mutations in the nuclear hormone receptor NR2E3, leading to progressive photoreceptor cell degeneration and significant vision loss.
Innovation Solution
Administration of nucleic acids encoding nuclear hormone receptors like Nr1d1, Nr2e3, Rora, Nupr1, or Nr2c1 to ocular tissues via electroporation or nanoparticle-based delivery systems, which modulate photoreceptor development and function, thereby rescuing clinical, morphological, and functional defects associated with NR2E3-associated retinal degeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for ocular diseases with retinal degeneration, then treatment options are limited, but disease progression and vision loss continue unabated
Solution Approach 1:
The patent introduces genetic modifiers as intermediary molecules that mediate between the mutant NR2E3 gene and the disease phenotype. These modifiers act as biological intermediaries that can either exacerbate or protect against retinal degeneration, providing a new therapeutic target that indirectly influences disease progression without directly correcting the primary mutation
Solution Approach 2:
The patent changes the therapeutic parameter from direct gene correction to modulation of downstream genetic modifiers. By targeting genes that regulate photoreceptor cell survival and function, the treatment alters the disease progression parameter through indirect genetic modulation rather than direct mutation correction
2Adaptability or versatility
If genetic modifiers are targeted for therapy, then new treatment options emerge, but delivery to ocular tissues becomes complex
Solution Approach 1:
Viral vectors serve as intermediary delivery vehicles that bridge the gap between the therapeutic genetic modifiers and the ocular tissues. These vectors act as mediators that simplify the delivery process by encapsulating and transporting the genetic material directly to target cells, reducing the complexity of direct gene delivery methods
Solution Approach 2:
The patent replaces complex mechanical delivery systems with biological vector-based delivery. Instead of using physical methods like electroporation or microinjection, the invention uses viral and non-viral vectors that naturally transport genetic material into cells, substituting mechanical complexity with biological efficiency
3Reliability
If photoreceptor function is restored through genetic modification, then visual function improves, but off-target effects may occur
Solution Approach 1:
The patent applies local quality by using tissue-specific promoters that drive expression of genetic modifiers only in photoreceptor cells. This ensures that the therapeutic effect is localized to the intended target cells, preventing off-target effects in other tissues while maintaining visual function restoration in the retina
Solution Approach 2:
The invention incorporates feedback mechanisms where the expression of genetic modifiers is regulated by endogenous signaling pathways in photoreceptor cells. This feedback control ensures that therapeutic protein expression occurs only when and where needed, automatically adjusting to maintain proper levels and minimize harmful off-target effects
Data Source
AI summary
The present invention relates to compositions and methods comprising administering gene modifiers for treating ocular disease.