Gene therapy by DNA methylation using CRISPR-Cas9

This 2016 Croatian human cell study was a proof-of-concept to induce specific DNA methylation of two genes:

“In this work we have created and characterized a novel CRISPR-Cas9-based epigenome editing tool, the dCas9-DNMT3A, which enabled targeted and specific CpG methylation at the promoter of two loci, the BACH2 and the IL6ST.

We have demonstrated the ability of the dCas9-DNMT3A construct to silence gene expression.

The BACH2 and IL6ST loci were previously associated with IgG glycosylation and inflammatory as well as autoimmune diseases.”

A few limitations:

“CpG methylation achieved using the active dCas9-DNMT3A construct was not stable in cultured cells. We found a ‘window’ of high methylation activity between days 5 and 15.

The relatively higher number of sgRNA [short complementary single guide RNA] targets in the BACH2 promoter compared to the IL6ST promoter (8 versus 4, respectively) might account for the higher statistical significance of gene silencing with inactive construct in the case of BACH2.” “Repurposing the CRISPR-Cas9 system for targeted DNA methylation”


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