CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations

The aim of this project was to investigate the extent and distribution of unintended mutations caused by CRISPR-Cas9 genome editing in vivo. To this end, we performed CRISPR-Cas9 genome editing of fertilized zebrafish eggs and analyzed on- and off-target effects in larvae, adult zebrafish, as well as their offspring. DNA samples from the zebrafish were analyzed using long-read sequencing technology, which facilitates detection of genomic structural variation induced by CRISPR-Cas9.