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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