CRISPR-Cas9 DNA cuts may disrupt the preservation of gene regulation signals

CRISPR-Cas9 double-strand breaks can cause stable, unintended DNA methylation changes at edited sites and other repaired breaks in human cells.

This genome-editing and epigenomics study used high-coverage long-read native DNA sequencing in hESCs and colorectal cancer cells to measure haplotype-resolved variants and base-resolution methylation after targeted DSBs.

The work is limited to in vitro cell systems and selected loci, so the frequency and consequences of these epigenetic disruptions in organisms or therapies remain uncertain.