[dnautics]

questions:

1) how would you get CRISPR into the brain?

2) how would you guarantee that nearly 100% of the target cells get it. The disease is a dominant condition, and by virtue of its putative mechanism a minority of untreated cells could still trigger the problem (though presumably onset might be delayed)

3) I would worry that if you do the CRISPR cut in the wrong place, or at the wrong time, you could instead make the tandem repeats even longer which would make the progression of the disease faster.

4) Outright deletion of the gene is -- who knows. AFAIK all humans have some, low number of tandem repeats and the disease emerges when you have a lot of tandem repeats. IIRC the mouse tandem repeat KO gene model has no side effects but stuff like alzheimer's AB being protective of certain viral brain infections is coming out, so maybe there's some function there? And lab mice aren't really exposed to too many pathogens.

[dnautics]

here's someone who did the deletion with CRISPR in the petri dish, and not on brain cells:

https://www.frontiersin.org/articles/10.3389/fnins.2018.0007...

and I correct myself, there is a phenotype to the deletion of the polglutamine track - the mice are dumber.

https://www.ncbi.nlm.nih.gov/pubmed/16403806/