{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["30"],"submitter":["Bastone AL"],"funding":["Deutsche Forschungsgemeinschaft","Lower Saxony State Ministry of Science and Culture","Horizon 2020"],"pubmed_abstract":["Safety assessment in retroviral vector-mediated gene therapy remains challenging. In clinical trials for different blood and immune disorders, insertional mutagenesis led to myeloid and lymphoid leukemia. We previously developed the <i>In Vitro</i> Immortalization Assay (IVIM) and Surrogate Assay for Genotoxicity Assessment (SAGA) for pre-clinical genotoxicity prediction of integrating vectors. Murine hematopoietic stem and progenitor cells (mHSPCs) transduced with mutagenic vectors acquire a proliferation advantage under limiting dilution (IVIM) and activate stem cell- and cancer-related transcriptional programs (SAGA). However, both assays present an intrinsic myeloid bias due to culture conditions. To detect lymphoid mutants, we differentiated mHSPCs to mature T cells and analyzed their"],"journal":["Molecular therapy. Methods & clinical development"],"pagination":["515-533"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10491817"],"repository":["biostudies-literature"],"pubmed_title":["Development of an <i>in vitro</i> genotoxicity assay to detect retroviral vector-induced lymphoid insertional mutants."],"pmcid":["PMC10491817"],"pubmed_authors":["Dittrich-Breiholz O","Dziadek V","Mansel F","Bastone AL","Fleischauer J","Schwarzer A","Schambach A","John-Neek P","Agyeman-Duah E","Rothe M","Schaudien D"],"additional_accession":[]},"is_claimable":false,"name":"Development of an <i>in vitro</i> genotoxicity assay to detect retroviral vector-induced lymphoid insertional mutants.","description":"Safety assessment in retroviral vector-mediated gene therapy remains challenging. In clinical trials for different blood and immune disorders, insertional mutagenesis led to myeloid and lymphoid leukemia. We previously developed the <i>In Vitro</i> Immortalization Assay (IVIM) and Surrogate Assay for Genotoxicity Assessment (SAGA) for pre-clinical genotoxicity prediction of integrating vectors. Murine hematopoietic stem and progenitor cells (mHSPCs) transduced with mutagenic vectors acquire a proliferation advantage under limiting dilution (IVIM) and activate stem cell- and cancer-related transcriptional programs (SAGA). However, both assays present an intrinsic myeloid bias due to culture conditions. To detect lymphoid mutants, we differentiated mHSPCs to mature T cells and analyzed their","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2026-05-28T15:28:34.679Z","creation":"2025-04-07T03:29:14.911Z"},"accession":"S-EPMC10491817","cross_references":{"pubmed":["37693949"],"doi":["10.1016/j.omtm.2023.08.017"]}}