High-throughput sequencing analysis of the integration pattern of MLV-derived gamma-retroviral vector in human JEB patient from pre-transplantation to 8 months follow-up.. Homo sapiens

We performed a high-throughput analysis of the integration pattern of MLV-derived gamma-retroviral vector in human JEB epidermal stem/progenitor cells pre and post transplantation of genetically modified epidermal graft. The integration profile was performed from 4 different time points obtained from six different samples: 3 samples from Pre Graft cultures (PGc), one from 4 months follow-up cultures (4Mc) and 2 different samples from 8 months follow-up cultures (8Mc1 and 8Mc2). We compared the high-throughput sequencing analysis derived from these samples in order to identify the integration profile and the specific selection of some integrations in vivo after patient treatment. This project shed light on the high-definition mapping of integration sites of vectors derived from the Moloney murine leukemia virus (MLV) in human epidermal cells, and revealed random profiles with no preferential tendency to target active regulatory regions. These data contribute to the evaluation of the risk of insertional mutagenesis of Moloney murine leukemia virus (MLV) vector in a clinical setting.