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Table 2 Summary table of TALE and CRISPR based targeted demethylation tools

From: DNA methylation and de-methylation using hybrid site-targeting proteins

Strategy Delivery Efficacy Duration Locus Peak site Editing range Target Off-targets Highlights Refs
TALE-TET1CD, TALE-TET1 Transfection ~ 15% 4 days KLF4
n.a. n.a. CpG Off-targets from unspeci_c binding First TALE-TE T study (2013) [53]
dCas9-TET1CD Transfection ~ 15% 24 h BRCA1 n.a. n.a. CpG Not detectable in LINE1 elements First dCas9-TE T study (2016) [56]
dCas9-TET1CD, MS2-TET1CD Transfection ~ 15% 4 days RANKL
n.a. ~ 500 bp by multi-sgRNAs CpG Not detectable at sgRN A similar sites MS2 coated sgRNA (2016) [57]
dCas-TET1CD Transduction ~ 26% 3 days Dazl-Snrpn n.a. n.a. CpG Minimal o ff-target on methylation and expression using dCas9-ChIP-BS-seq and RNA-seq Induce an active chromatin status for promote r.
Sustainable in a human/mouse chimeric model (2016)
[40, 58]
dCas9-Sun Tag-TET1CD Transfection ~ 80% 2 days Gfap
n.a. 200–1000 bp CpG Not detectable (WGBS; RNA-seq) Long range demethylation.
In vivo delivery by in utero electroporation (2016)
Gal4-ROS1 CD Transfection n.a. 2 days Reporter plasmid n.a. n.a. CpG n.a. Direct removal of 5mC without hydroxymethylation (2017) [59]