Moloney Murine Leukemia Virus Based Retroviral Vector

Another member of the genera retroviridae commonly studied in gene therapy is the amphotropic MLV-based retrovirus (Romano et al. 1999; Shinnick et al. 1981; Weiss 1998; Weiss and Wrangham 1999). MLV-based retroviral vectors contain a single-stranded, linear, positive-sense RNA molecule of approximately 8000 nucle-otides. In some studies in utero, MLV-based retroviral vectors have been pseudo-typed with VSV-G envelope proteins (Tarantal et al. 2001). MLV-based retroviral vectors infect dividing cells and integrate into the host cell genome providing the rationale that MLV-based retroviral vectors could offer permanent gene replacement in utero (Miller et al. 1990). While studies have shown short term expression in canine mucopolysaccharidosis Type I animal models, they have not demonstrated long term gene expression and transgene integration into the germ line (Meertens et al. 2002).

Relatively few retroviral in utero studies transducing muscle tissues have been performed. One study showed prenatal systemic delivery of an MLV-based retrovi-ral vector that exhibited expression in various tissues with minimal expression in the muscles (Tarantal et al. 2001). The low transduction efficiency, the requirement of dividing cells and instability in the presence of body fluids are significant limitations of the MLV-based retroviral vector for in vivo muscle gene transfer. Furthermore, in recent years a study demonstrated premalignant proliferation and lymphoproliferative disease in an X-SCID trial in which study participants received transplantation of retroviral vector-transduced, autologous bone marrow-derived CD34+ cells (Hacein-Bey-Abina et al. 2003). The potential for malignant transformation is a significant concern that is heightened for in utero application.

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