[Spacecosmonaut]

I'm a genetic engineer at a large pharma company. We corrected the HTT gene in patient derived iPSCs in the lab. The region is a long repeat sequence of which a section needs to be deleted. Because of this the locus is quite difficult to genetically engineer, since it is difficult to target just the diseased allele but not the wild-type allele.

Typical gene therapeutic approaches probably wont work, e.g. Cas9 (you'd need two cuts to delete the sequence), Base editors (cant delete sequence), prime editing (deletion is too large for standard prime editing).

You'd either need a template based system such as homologous recombination (too inefficient) or something like twin-prime editing, but good luck getting that to work on repeat sequence.