New publication in "International Journal of Molecular Science"
Targeted DNA methylation is a promising approach for the modulation of gene expression in basic research and in the clinic. However, it often suffers from a lack of specificity, because off-target regions also are methylated. We have rationally designed different DNMT3A variants with reduced DNA binding and applied them for targeted methylation. Our data show that this leads to a pronounced improvement in the specificity of targeted DNA methylation as indicated by a strongly reduced off-target methylation accompanied by an only mild reduction of on-target activity. These improved DNMT3A variants will advance the future applications of this emerging technology.