>>13318270I guess the most "straightforward" way would be just to use Cas9 with gRNA specific to the STR sequences of the victim, along with Donor DNA coding for some toxic protein.
The Cas9 would snip at the right spot, and the DNA would get integrated via HDR. This way, you could also make it truly specific for STR length by having the donor DNA be compatible with the first and the last STR triplet, along with the non-STR bases in front of the first triplet and after the last one.
One problem here is that, since STR regions are non-coding, you'd have to include your own promoters with the donor DNA, which would be a huge hassle because if you want your gene expressed in any significant quantity you'd also have to include the proximal promoters which are easily 200 BPs away from the actual gene.
Another problem is that targeting just one STR sequence wouldn't be enough. To truly be specific, you'd have to target a lot of them, which means having to design unique Cas9/gRNA complexes for each one.
And then, you'd somehow have to achieve that the toxic protein is only expressed if all the STR sequences are there (meaning that you have the right person).
I really don't know about this part. Maybe you could have the different parts express different sub-units of a protein, which would then be assembled by the cell itself, idk tho.
