GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE267nnn/GSE267768/primary200OKOther Mus musculusHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267768GEOGSEfalseGenuine-seq enables genome-wide unbiased identification of off-target cleavage and translocation by CRISPR nucleasesCRISPR-Cas system is one of the most widely used tool kit for genome editing. In practice, CRISPR’s causes chromosomal structural variation due to off-targets, which is a serious genotoxicity, while currently unbiased methods for detecting chromosomal structural variation are largely lacking. Here, we developed Genome-wide ubiased identification of nuclease effects by sequencing (Genuine-Seq), which could detect both off-target sites of CRISPR and chromosomal structural variations caused by off-target effects, including translocations and large deletions. We demonstrated Genuine-seq’s high efficiency in human cells, and compared spCas9 and spRY, emphasizing that spRY can cause tremendous off-target cutting. Using mouse models, we performed in vivo experiments to depict the landscape of off-target sites and chromosomal structural variations caused by CRISPR-Cas editing, which demonstrated the translational value of Genuine-seq in safety assessment of CRISPR-based therapeutics.2026/09/26GSE267768GSM8275420GSM8275421GSM8275422GSM8275423GSM8275424GSM8275425GSM8275426GSM8275416GSM8275417GSM8275418GSM8275419GSM8275430GSM8275397GSM8275431GSM8275398GSM8275399GSM8275432GSM8275433GSM8275434GSM8275435GSM8275436GSM8275437GSM8275395GSM8275396GSM8275427GSM8275428GSM8275429GSM8275441GSM8275442GSM8275443GSM8275400GSM8275444GSM8275445GSM8275401GSM8275402GSM8275446GSM8275403GSM8275447GSM8275448GSM8275404GSM8275440GSM8275438GSM8275439GSM8275452GSM8275453GSM8275410GSM8275454GSM8275411GSM8275455GSM8275412GSM8275413GSM8275414GSM8275415GSM8275450GSM8275451GSM8275405GSM8275449GSM8275406GSM8275407GSM8275408GSM82754093428434290267768 Mus musculusHomo sapiens