CRISPR-Cas9 Editing of CEP290 Gene via AAV Vectors

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for Leber's Congenital Amaurosis 10 (LCA10), a severe inherited retinal degenerative disease, lack effective therapeutics despite advances in gene therapy, as controlling expression levels of therapeutic genes remains a challenge.

Innovation Solution

The use of CRISPR-Cas9 mediated genome editing systems, specifically delivering nucleic acids encoding Cas9 and guide RNAs targeted to the CEP290 gene via adeno-associated viral vectors for efficient transduction and editing in retinal cells, aiming to restore CEP290 function and alter the CEP290 gene sequence to address the underlying mutation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gene augmentation therapy is used to treat LCA, then therapeutic gene expression can be achieved, but controlling expression levels of the therapeutic genes becomes difficult

Engineering Contradiction:

Improvetherapeutic gene expressionVSAvoidexpression level control

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical/vector-based gene delivery system (AAV vectors) with a CRISPR-Cas9 genome editing system that directly modifies the endogenous CEP290 gene. This substitution eliminates the need for external therapeutic gene expression control by instead repairing the patient's own gene, thereby resolving the contradiction between achieving therapeutic expression and controlling its levels.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Manufacturing precision

If CRISPR-Cas9 genome editing is used to edit CEP290 gene, then precise gene sequence alteration can be achieved, but efficient delivery to retinal cells becomes challenging

Engineering Contradiction:

Improvegene sequence editing precisionVSAvoiddelivery efficiency to retinal cells

Core Design Contradiction:

Manufacturing precisionVSEase of operation

Solution Approach 1:

The patent uses adeno-associated virus (AAV) vectors as intermediary carriers to deliver the CRISPR-Cas9 editing machinery into retinal cells. The AAV vector serves as a mediator that bridges the gap between the precise genome editing system and the difficult-to-transduce retinal tissue, thereby resolving the contradiction between editing precision and delivery efficiency.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11339437B2Compositions and methods for treating CEP290-associated disease

Publication Date: 2022.05.24 EDITAS MEDICINE INC

AI summary

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