{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326932"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Genotoxicity profiling reveals distinct platform- and cell type–specific effects in therapeutic gene editing for genetic hyperinflammation","description":"Base 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.","dates":{"publication":"2026/04/03"},"accession":"GSE326932","cross_references":{"GSM":["GSM9643751","GSM9643773","GSM9643774","GSM9643752","GSM9643771","GSM9643772","GSM9643750","GSM9643770","GSM9643737","GSM9643759","GSM9643738","GSM9643757","GSM9643735","GSM9643779","GSM9643758","GSM9643736","GSM9643777","GSM9643755","GSM9643778","GSM9643756","GSM9643775","GSM9643753","GSM9643754","GSM9643776","GSM9643739","GSM9643762","GSM9643740","GSM9643763","GSM9643741","GSM9643760","GSM9643761","GSM9643780","GSM9643781","GSM9643748","GSM9643749","GSM9643768","GSM9643746","GSM9643769","GSM9643747","GSM9643766","GSM9643744","GSM9643745","GSM9643767","GSM9643742","GSM9643764","GSM9643765","GSM9643743"],"GPL":["24247"],"GSE":["326932"],"taxon":["Mus musculus"]}}