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It seems from the replies that the C9orf mutation in more common for our online community. I was expecting some with the SOD1 – was hoping for more SOD1 since there is a treatment available and more treatments on the forefront of research.
My doctor explained why the C9 mutation was more difficult to address in the treatments. The science is a bit over my head, but if I recall correctly it had to do with it being more difficult because the mutation repeats.
“The C9orf72 (C9) repeat expansion is generally considered more challenging to edit using gene editing techniques like CRISPR-Cas9 than the SOD1 mutation primarily <mark style=”font-family: inherit; font-size: inherit;”>due to the nature of the mutation and the technical difficulties in targeting and correcting it</mark>. C9 mutations involve large, variable expansions of a specific DNA sequence, while SOD1 mutations are single point mutations.
Here’s a more detailed breakdown:
Challenges with C9orf72:
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Large Repeat Expansions:
C9 mutations involve hundreds or even thousands of repeats of a DNA sequence, making it difficult to target and edit with precision.
DNA Low Complexity:
The region surrounding the C9orf72 expansion has low complexity, increasing the risk of off-target effects (editing unintended locations in the genome).
Difficulty in Identifying and Correcting Expansions:
Traditional sequencing methods are inadequate to accurately size large repeat expansions, and detecting C9orf72 RNA and protein products can be challenging.
Technical Hurdles with CRISPR-Cas9:
The large size of the repeat expansions and the surrounding low-complexity region make it challenging to design effective CRISPR-Cas9 systems that can target and correct the mutation without causing unintended edits.
SOD1 Mutations are Easier to Edit:
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Single Point Mutations:
SOD1 mutations are usually single point mutations, making it easier to target with CRISPR-Cas9.
Established Target Sites:
The SOD1 gene is well-studied, and there are established target sites for gene editing, making it easier to design effective CRISPR-Cas9 systems.
More Efficient Targeting:
Single point mutations are easier to target and correct with CRISPR-Cas9, leading to higher editing efficiency.
In Summary:
The C9orf72 repeat expansion is more difficult to edit due to its large size, the surrounding low-complexity DNA, and the technical challenges in accurately targeting and correcting the mutation with gene editing tools like CRISPR-Cas9. SOD1 mutations, being single point mutations, are generally easier to target and edit.” (from google search)
Here is an article that might help some — https://pmc.ncbi.nlm.nih.gov/articles/PMC5880162/#:~:text=When%20comparing%20mutation%20rates%20of,2013).