Cone Photoreceptor Gene Therapy With AAV8 and M-Opsin Promoter

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for therapies that can improve cone survival and function to treat or prevent retinal disorders such as cone-rod dystrophies and age-related macular degeneration, as cone dysfunction leads to significant visual impairment and photophobia.

Innovation Solution

The use of nucleic acids, transcriptional control units (TCUs), optimized gene sequences, and vectors, including an M-opsin promoter and AAV8 vectors, to drive high expression levels of essential genes like CNGA3 in cone photoreceptors, enhancing cone function and survival.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional gene delivery methods are used, then gene expression is achieved, but expression levels are insufficient to rescue cone function

Engineering Contradiction:

Improvegene expression levelVSAvoidcone function rescue

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent optimizes multiple parameters of the gene delivery system including promoter strength (using M-opsin promoter), vector choice (AAV8), codon optimization of the CNGA3 gene, and transcriptional control unit design to achieve high-level sustained expression necessary for functional rescue

Inventive Principle:

Principle #35Parameter changes

2Reliability

If high levels of gene expression are achieved, then cone function is rescued, but the complexity of the gene delivery system increases

Engineering Contradiction:

Improvecone function rescueVSAvoidgene delivery system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a multi-functional transcriptional control unit that combines promoter, enhancer, and regulatory elements into a single integrated construct that achieves both high expression and cone-specific targeting through the M-opsin promoter

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses AAV8 vectors as intermediary carriers that naturally target retinal cells, simplifying the delivery mechanism while achieving efficient gene transfer to cone photoreceptors

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If cone photoreceptors are lost or dysfunctional, then visual acuity deteriorates, but existing therapies cannot prevent cone loss

Engineering Contradiction:

Improvevisual acuityVSAvoidcone survival time

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent delivers the functional CNGA3 gene before complete cone loss occurs, allowing the restored protein function to prevent apoptotic pathways and maintain cone survival long-term

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent converts the harmful effect of CNGA3 deficiency (cone dysfunction and death) into a benefit by delivering a functional copy of the gene that not only restores function but also triggers protective cellular responses that extend cone survival

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS12467066B2Compositions and methods for treating retinal disorders

Publication Date: 2025.11.11 UCL BUSINESS LTD

AI summary

The present invention relates to the prevention and/or treatment of retinal disorders, such as cone dystrophies, cone-rod dystrophies, in particular Achromatopsia.