The discovery and adaptation of the CRISPR/Cas system for epigenome editing has allowed for a straightforward design of targeting modules which can direct epigenetic editors to virtually any genomic site. This advancement in DNA-targeting technology brings allele-specific epigenome editing into reach, a "super-specific" variation of epigenome editing whose goal is an alteration of chromatin marks at only one selected allele of the target genomic locus. This technology would be useful for the treatment of diseases caused by a mutant allele with a dominant effect, because allele-specific epigenome editing allows the specific silencing of the mutated allele leaving the healthy counterpart expressed. Moreover, it may allow the direct correction of aberrant imprints in imprinting disorders where editing of DNA methylation is needed in one allele only. Here, we describe some principal setups of allele-specific epigenome editing systems and present exemplary data illustrating the feasibility of the concept.
Keywords: Allele-specific editing; CRISPR/dCas9; DNA methylation; Epigenome editing; Imprinting.