GEOOtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326932GEOGSEfalseGenotoxicity profiling reveals distinct platform- and cell type–specific effects in therapeutic gene editing for genetic hyperinflammationBase editors enable precise correction of point mutations without requiring DNA double-strand breaks, yet platform– and cell type–specific genotoxicities remain incompletely characterized. Here, we applied cytosine base editing (CBE) to disrupt a cryptic splice-site mutation in the Unc13d locus of Jinx mice, a model of familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Efficient editing (62–89%) in fibroblasts, T cells, and hematopoietic stem cells (HSCs) restored Unc13d splicing, reconstituted cytotoxic T cell function, and protected mice from virus-triggered hyperinflammation after transplantation of edited HSCs. Comparative genotoxicity profiling revealed distinct platform- and cell type–specific patterns: hyperactive CBE induced broader off-target activity and more structural variants than CRISPR–Cas9. While off-target sequence edits persisted, the stability of CBE-induced chromosomal translocations differed between cell types. These findings establish therapeutic base editing for a genetically predisposed hyperinflammatory syndrome and underscore the importance of context-specific safety profiling to guide clinical translation of genome editors.2026/04/03GSE326932GSM9643751GSM9643773GSM9643774GSM9643752GSM9643771GSM9643772GSM9643750GSM9643770GSM9643737GSM9643759GSM9643738GSM9643757GSM9643735GSM9643779GSM9643758GSM9643736GSM9643777GSM9643755GSM9643778GSM9643756GSM9643775GSM9643753GSM9643754GSM9643776GSM9643739GSM9643762GSM9643740GSM9643763GSM9643741GSM9643760GSM9643761GSM9643780GSM9643781GSM9643748GSM9643749GSM9643768GSM9643746GSM9643769GSM9643747GSM9643766GSM9643744GSM9643745GSM9643767GSM9643742GSM9643764GSM9643765GSM964374324247326932Mus musculus