CEP290 Genome Editing in Retinal Cells for Controlled Expression

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Solution Overview

Problem

There are currently no effective therapeutics for Leber's Congenital Amaurosis 10 (LCA10), a severe form of inherited retinal dystrophy caused by mutations in the CEP290 gene, and existing gene therapy methods struggle with controlling expression levels.

Innovation Solution

Delivery of genome editing systems, specifically using CRISPR/Cas9 technology, to target and edit the CEP290 gene in retinal cells through adeno-associated viral vectors, such as AAV5, to correct mutations and restore functional CEP290 protein expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gene augmentation therapy is used to treat CEP290-associated diseases, then therapeutic gene expression can be introduced, but the expression levels of the therapeutic genes cannot be controlled

Engineering Contradiction:

Improvetherapeutic gene expressionVSAvoidexpression level control

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent uses CRISPR/Cas9 genome editing technology to precisely modify the CEP290 gene at the DNA level, changing the genetic parameter to restore functional protein expression. This approach provides reliable and sustained therapeutic effect without the expression control issues of gene augmentation therapy, as the edited gene naturally regulates its own expression levels through endogenous promoters and regulatory elements.

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If CRISPR/Cas9 genome editing is used to target CEP290 gene, then precise mutation correction can be achieved, but delivery to retinal cells presents technical challenges

Engineering Contradiction:

Improvemutation correction precisionVSAvoiddelivery system complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent employs adeno-associated viral vectors (AAV) as intermediary delivery vehicles to transport the CRISPR/Cas9 components into retinal cells. The AAV vector serves as a mediator that protects the genetic material during delivery, enables efficient transduction of hard-to-transfect retinal cells, and reduces immunogenicity, thereby solving the delivery challenge while maintaining editing precision.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If existing gene therapy methods are used for CEP290-associated diseases, then some therapeutic effect can be achieved, but expression levels cannot be controlled leading to potential adverse effects

Engineering Contradiction:

Improvetherapeutic effectVSAvoidadverse effects from uncontrolled expression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The CRISPR/Cas9 genome editing approach enables the CEP290 gene to serve itself by restoring its natural ability to regulate expression levels. The edited gene uses its own endogenous promoter and regulatory sequences to control transcription, ensuring that therapeutic protein levels remain within physiological ranges without causing overexpression-related adverse effects.

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS20260034247A1Compositions and methods for treating CEP290-associated disease

Publication Date: 2026.02.05 EDITAS MEDICINE INC

AI summary

Compositions and methods for treatment of CEP290 related diseases are disclosed.