CRISPR/Cas MYOC Editing for Long-Term POAG Control

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Solution Overview

Problem

Current treatments for Primary Open Angle Glaucoma (POAG) are inadequate in providing a one-time or several-dose treatment that effectively reduces intraocular pressure and prevents the progression of the disease, as they are either invasive or have limited efficacy in managing the underlying genetic causes.

Innovation Solution

The use of CRISPR/Cas systems to target and alter the MYOC gene, specifically through homology-directed repair (HDR) or non-homologous end joining (NHEJ), to knockout or knockdown the expression of mutated MYOC gene products, thereby addressing the genetic causes of POAG.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If trabeculectomy surgery or eye drops are used to reduce intraocular pressure, then IOP reduction is achieved, but the treatment requires continuous intervention and does not address the underlying genetic cause

Engineering Contradiction:

Improvedisease prevention efficacyVSAvoidtreatment convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The CRISPR/Cas9 system performs preliminary genetic correction by targeting and modifying the mutated MYOC gene before disease progression occurs. The guide RNA directs the Cas9 endonuclease to the specific mutation site, where it creates a double-strand break that triggers homology-directed repair, permanently correcting the genetic defect that causes POAG. This preliminary genetic intervention eliminates the need for continuous symptomatic treatment.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent replaces mechanical/surgical interventions (trabeculectomy) and chemical interventions (eye drops) with a molecular-level genetic editing system. The CRISPR/Cas9 mechanism substitutes physical surgery and ongoing pharmacological treatment with a precise molecular scissors system that directly corrects the genetic blueprint, transitioning from treating symptoms to correcting the root genetic cause.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If current POAG treatments are used, then intraocular pressure is reduced temporarily, but the disease progresses and requires lifelong management

Engineering Contradiction:

Improvelong-term disease controlVSAvoidcontinuous treatment duration

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The CRISPR/Cas9 system enables self-service by correcting the patient's own genetic defect. The guide RNA is designed to match the patient's specific MYOC mutation, and the Cas9 endonuclease repairs the patient's own genome through homology-directed repair using a provided template. This self-correcting mechanism addresses the root cause permanently, eliminating the need for lifelong external intervention and allowing the body to maintain healthy IOP regulation autonomously.

Inventive Principle:

Principle #25Self-service

3Productivity

If genetic correction of MYOC mutations is attempted, then a one-time curative treatment is achieved, but the complexity of CRISPR/Cas9 delivery and precision targeting increases

Engineering Contradiction:

Improvetreatment efficiencyVSAvoidgene editing system complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The CRISPR/Cas9 system is segmented into distinct functional modules: the guide RNA (gRNA) module for target recognition, the Cas9 endonuclease module for DNA cleavage, and the homology-directed repair template for precise correction. This segmentation allows each component to be optimized independently and facilitates delivery through various vectors. The modular nature reduces overall system complexity by making each element's function specialized and interchangeable.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The guide RNA serves as an intermediary that bridges the gap between the Cas9 endonuclease and the specific MYOC mutation target. The gRNA contains a spacer sequence complementary to the mutant MYOC allele, allowing it to direct Cas9 precisely to the mutation site without requiring complex targeting mechanisms. This simple RNA-mediated targeting intermediary dramatically simplifies the overall system compared to alternative gene editing approaches that would require complex protein-protein interaction networks for specificity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach potentially offers a one-time treatment by correcting the genetic mutations causing POAG, reducing intraocular pressure and preventing disease progression, thus providing a more effective and less invasive method for managing the condition.