Figure 5.

Cumulative mutant specificity of TP-CRISPR strategies using PAS

To calculate the proportion of HD subjects who are eligible for mutant HTT-specific TP-CRISPR strategies using one allele-specific gRNA and one non-allele-specific gRNA, we analyzed phased allele data for 224 PAS. For the initial coverage analysis, we identified HD subjects who carry the PAM site only on the mutant HTT and calculated the proportion of those HD subjects. Then, we re-calculated the mutant specificity in the remaining HD subjects to identify the PAS with the highest mutant specificity. We repeated these procedures 10 times to estimate the cumulative mutant specificity of the allele-specific TP-CRISPR strategies.