Sensitive and unbiased genome-wide profiling of base-editor-induced off-target activity with CHANGE-seq-BE [CHANGE-seq-BE for CD40L target]

By CHANGE-seq-BE, we identified a total of 81 potential off-targets and confirmed 95.4% frequencies of on-target editing with no evident off-targets above the detection threshold compared to controls (rhAmp-seq, IDT). Overall design: CHANGE-seq-BE applied as an IND-enabling assay to support an emergency FDA-cleared IND study to treat a patient with X-linked Hyper IgM syndrome due to CD40L mutation.