Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment
We propose single cell DNA sequencing (scDNAseq) to longitudinally evaluate ON-target genotoxicity induced by CRISPR-Cas9 in clinically relevant cells. By focusing on SNP (single nucleotide polymorphism) and copy number variations (CNV) analyses, we demonstrate that scSNP-DNAseq is a powerful assay to measure chromosomal instability following CRISPR editing, in particular CN-LOHs with high sensitivity, in vitro and in vivo.