Comment by amluto
2 days ago
Surely a far simpler way to evolve resistance would be a trivial mutation in the p53 transcript that the guide RNA is looking for.
2 days ago
Surely a far simpler way to evolve resistance would be a trivial mutation in the p53 transcript that the guide RNA is looking for.
In practice, you’d use multiple guides targeting multiple mutations, so that the probability of having/acquiring multiple resistance mutations abrogating every guide from binding would be infinitesimal.
LNPs have limited capacity, and if the CRISPR/Cas system they’re using requires an exact match, then any additional point mutation or insertion or deletion in the segment being matched would allow the cell to survive. I suppose that approximately 3n extra guide RNAs (where n is the length of the matched sequence) could be added, but that seems a bit messy.
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