Themis, MikeWaddington, Simon NSchmidt, Manfredvon Kalle, ChristofWang, YoaheAl-Allaf, FaisalGregory, Lisa GNivsarkar, MeghaThemis, MatthewHolder, Maxine VBuckley, Suzanne M KDighe, NirajaRuthe, Alaine TMistry, AjayBigger, BrianRahim, AhadNguyen, Tuan HTrono, DidierThrasher, Adrian JCoutelle, Charles2005-09-052005-09-052005-09-05200510.1016/j.ymthe.2005.07.358https://infoscience.epfl.ch/handle/20.500.14299/215903Gene therapy by use of integrating vectors carrying therapeutic transgene sequences offers the potential for a permanent cure of genetic diseases by stable vector insertion into the patients' chromosomes. However, three cases of T cell lymphoproliferative disease have been identified almost 3 years after retrovirus gene therapy for X-linked severe combined immune deficiency. In two of these cases vector insertion into the LMO2 locus was implicated in leukemogenesis, demonstrating that a more profound understanding is required of the genetic and molecular effects imposed on the host by vector integration or transgene expression. In vivo models to test for retro- and lentiviral vector safety prior to clinical application are therefore needed. Here we present a high incidence of lentiviral vector-associated tumorigenesis following in utero and neonatal gene transfer in mice. This system may provide a highly sensitive model to investigate integrating vector safety prior to clinical application.text::journal::journal article::research article