Extended Data Fig. 2: Evaluation of candidate ZFPs in HdhQ111/HdhQ7 striatal cells and HD fibroblasts.
From: Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease
a,b, Comparison of allele selectivity exhibited by candidate ZFP-TF designs in (a) the mouse cells used in a previous study27 (striatal cells derived from the HdhQ111/HdhQ7 mouse model, CAG111/4) versus (b) the human HD fibroblast screening system used in the current study (GM02151, CAG18/45). Only three tested designs (ZFP-A, -B and -D) exhibit highly allele-selective repression in the human HD fibroblast system (>75% repression of the mutant allele with <10% repression of the WT allele, denoted by green circles). In contrast, 25 designs manifest such behavior in the less stringent mouse cells. n = 3 biologically independent samples; mean ± s.d. c, Evaluation of endogenous mHTT allele selectivity for the CAG-targeted ZF6xHunt–Kox-1 (ZF6) and ZF11xHunt–Kox-1 (ZF11) from ref. 27 in GM02151 fibroblasts. Normalized transcript levels for normal (CAG18, blue), mutant (CAG45, red) and total HTT (gray) in fibroblasts transfected with 1,000, 300 or 100 ng ZFP or GFP mRNA. M, mock transfection. n = 4 technical replicates; mean ± s.d.
