CRISPR Editing of USH2A IVS40 Mutation for Usher Syndrome
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Solution Overview
Problem
There are currently no adequate treatments for Usher Syndrome that can efficiently halt or slow the progression of the visual loss associated with the disease.
Innovation Solution
A novel method involving the use of CRISPR endonucleases to edit the USH2A gene in human cells, specifically targeting and correcting the IVS40 mutation by introducing single-strand or double-strand breaks, thereby disrupting incorrect splicing and potentially eliminating the disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for Usher Syndrome, then patient safety is maintained, but the progression of visual loss cannot be halted or slowed
Solution Approach 1:
The patent extracts and removes the harmful IVS40 mutation from the USH2A gene using CRISPR-Cas9 technology. The guide RNA specifically targets the mutated intron 40 region, and the Cas9 endonuclease cleaves the DNA at this location, excising the harmful splice donor site sequence that causes incorrect splicing and disease progression.
Solution Approach 2:
The patent replaces conventional pharmacological or supportive treatments with a precise molecular editing system. Instead of using drugs or devices that manage symptoms, the invention uses CRISPR-Cas9 molecular machinery to directly edit the genetic code, substituting a mechanical/biochemical approach with a targeted genomic intervention.
2Manufacturing precision
If multiple treatments are administered to edit the USH2A gene, then correction accuracy improves, but treatment complexity and time increase
Solution Approach 1:
The patent designs the CRISPR-Cas9 system with predetermined guide RNA sequences that are pre-calculated to target the specific IVS40 mutation. The sgRNA is engineered beforehand with the exact 20-nucleotide spacer sequence complementary to the mutated region, allowing the system to achieve high precision in a single administration without requiring iterative corrections.
Solution Approach 2:
The patent employs a universal CRISPR-Cas9 platform that can address the IVS40 mutation through a single multi-functional system. The Cas9 endonuclease works with the guide RNA to simultaneously achieve DNA binding, cleavage, and initiation of repair mechanisms, consolidating multiple editing functions into one treatment event rather than requiring separate steps for each function.
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
The method has the potential to ameliorate or eliminate Usher Syndrome Type 2A associated with an IVS40 mutation, with some cases requiring only a single treatment.
Implementation Method 1
introducing into the human cell one or more deoxyribonucleic acid (DNA) endonuclease, thereby effecting one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the USH2A gene
Data Source
AI summary
The present application provides materials and methods for treating a patient with Usher Syndrome Type 2A, both ex vivo and in vivo; materials and methods for editing a USH2A gene in a human cell; materials and methods for editing an USH2A gene containing an IVS40 mutation; materials and methods for treating a patient with an USH2A gene containing an IVS40 mutation; and a method for deleting a sequence comprising an IVS40 mutation within a USH2A gene of a cell. The present application also provides one or more gRNAs or sgRNAs for editing an USH2A gene containing an IVS40 mutation. The present application provides a therapeutic for treating a patient with Usher Syndrome Type 2A. The present application also provides a kit for treating a patient with Usher Syndrome Type 2A.