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Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice.

Themis, M, Waddington, S, Schmidt, M, von Kalle, C, Wang, Y, Al-Allaf, F, Gregory, L, Nivsarkar, M, Themis, M, Holder, M, Buckley, S, Dighe, N, Ruthe, A, Mistry, A, Bigger, B, Rahim, A, Nguyen, T, Trono, D, Thrasher, A, Coutelle, C

Molecular Therapy. 2005;12( 4):763-71.

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Gene 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.

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United States
12( 4)
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2nd September, 2009, 09:26:53
Last modified:
17th November, 2012, 18:24:35

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