CRISPR-Cas9 Editing of DMD Gene Exons for Muscular Dystrophy
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Solution Overview
Problem
Current gene therapy approaches for Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and dilated cardiomyopathy type 3B face challenges due to the large size of the DMD gene, with delivery and long-term efficacy issues, requiring frequent intramuscular injections and compromising therapy effectiveness.
Innovation Solution
The use of CRISPR-Cas9 mediated genome-editing systems to introduce breaks in the DMD gene, allowing for break-induced deletions or indels, thereby altering the dystrophin sequence to restore a correct reading frame, using gRNAs to target specific positions and Cas9 nucleases to create single or double strand breaks, avoiding unwanted chromosome elements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current gene therapy approaches are used to treat DMD, then the DMD gene can be targeted, but the large size of the DMD gene causes delivery issues and requires frequent intramuscular injections
Solution Approach 1:
The patent extracts and targets only the specific mutated exon region of the DMD gene using CRISPR-Cas9, rather than attempting to deliver or edit the entire 2.2 megabase gene. This extraction of the critical target region enables effective treatment without the delivery limitations imposed by the gene's full size, reducing the need for frequent administrations.
2Reliability
If current gene therapy approaches are used for DMD, then treatment can be provided, but delivery issues arise due to the large size of the DMD gene
Solution Approach 1:
The invention extracts the essential therapeutic function to targeting and editing only the specific mutated exon sequence within the DMD gene. This reduces the complexity of the delivery system by eliminating the need to deliver the entire large gene, focusing instead on delivering only the CRISPR-Cas9 components needed to address the specific mutation.
Solution Approach 2:
The patent segments the DMD gene editing task into targeting only the specific mutated exon region rather than the entire gene. This segmentation allows the use of smaller, more manageable CRISPR-Cas9 delivery systems that can effectively reach and edit the specific target without the complexity of delivering the full 2.2 megabase gene.
3Duration of action of stationary object
If frequent intramuscular injections are administered, then therapy can be maintained, but long-term efficacy is compromised
Solution Approach 1:
The CRISPR-Cas9 system performs preliminary genetic editing to correct the mutated exon sequence, establishing a permanent fix that eliminates the need for repeated treatments. This preliminary correction action addresses the root cause of the disease at the genetic level, providing long-lasting efficacy without requiring frequent maintenance injections.
Solution Approach 2:
The genetic correction achieved through CRISPR-Cas9 editing enables the cell's own machinery to produce functional dystrophin protein from the corrected gene sequence. This self-service mechanism allows the body to continuously produce the necessary protein without external intervention, maintaining long-term efficacy without frequent administrations.
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 delays the onset or progression of these diseases by altering the DMD gene, providing a more effective and sustainable treatment option compared to existing therapies, with the potential for reduced frequency of administration and improved long-term efficacy.
Implementation Method 1
The use of CRISPR-Cas9 mediated genome-editing systems to introduce breaks in the DMD gene, allowing for break-induced deletions or indels, thereby altering the dystrophin sequence to restore a correct reading frame
Data Source
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AI summary
CRISPR/CAS-related compositions and methods for treatment of DMD, BMD, or DCM type 3B are described.