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Table 1 Summary table of TALE and CRISPR based targeted methylation tools

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

Strategy Delivery Efficacy Duration Locus Peak site Editing
range
Target Off-targets Features Refs
TALE-DNMT3ACD-3 L Transfection
Transduction
12–15%
17%
2 days
4 days
CDKN2A n.a. ~ 700 bp CpG At nearby regions (Targeted mePCR) First TALE-DNMT3 A study (2015) [33]
TALE-CIB1; DNMT3A/TET1 CD-C R Y2 Transfection ~ 10% ~ 5 days Ascl 1 n.a. n.a. CpG n.a. Epigenome editing by optogenetics (2017) [34]
dCas9-DNMT3ACD Transfection ~ 35%
~ 43%
8 days
3 days
BACH2
CDKN2A
−27 bp, + 25 bp < 100 bp CpG Off-targets observed using unspeci_c sgRNAs First dCas9-DNMT3 A studies (2016) [38, 39]
dCas9-DNMT3A Transduction ~ 12%
~ 25%
3 days
3 days
Gapdhsnrpn
CDKN2A
n.a. n.a. CpG Not detectable (dCas9 ChIP-seq) Targeted methylation alters CTCF looping and local genes expression (2016) [40]
TALE/dCas9-KRAB, DNMT3ACD, DNMT3L Transduction ~ 80% 30 days B2M n.a. ~ 3 kb CpG Not detectable (MeDIP-seq) Inheritable silencing of endogenous genes (2016) [43]
dCas9-DNMT3ACD-3 L Transfection ~ 30% 5 days TFRC
CXCR4
−40 bp, + 25 bp ~ 800 bp CpG Mild off-target observed More e_cient than dCas9- DNMT3ACD (2016) [44]
dCas9-Sun Tag-DNMT3A Transduction ~ 70%
~ 45%
30 days HOXA5
DLX1
n.a. ~ 4.5 kb
~ 500 bp
CpG (CpH) Not detectable (RRBS; WGBS) Long range methylation Non-CpG methylation (2017) [47]
dCas9-Sun Tag-DNMT3ACD Transfection ~ 15% 4 days UNC5C n.a. n.a. CpG Not detectable (TSC-bs-seq) Modular Sun Tag- DNMT3ACD reduces off-target events (2018) [62]
dCas9-MQ1 147 Transfection *60% 24 h HOXA5
HOXA4
RUNX1
−24-26 bp n.a. CpG Not detectable (RRBS) In vivo application using
zygote injection (2017)
[54]
dCas9-split M.SssI Transfection *50% 2 days SALL2 −22-23 bp 8–25 bp CpG Not detectable (Targeted mePCR) Split catalytic domain for
higher speci_cty (2017)
[48]
  1. *Maximum DN A methylation at a CpG