Attempt for gene therapy of retrovirus-induced disease

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To develop the model for gene therapy of retrovirus-induced disease, Fv-4 resistance (Fv-4^r) gene which confers strong resistance against murine leukemia virus (MuLV)-infection to host has been introduced to Friend leukemia virus (FLV)-susceptible C3H mouse bone marrow cells.1) Bone marrow transplantation of Fv-4^r-transfected bone marrow cells to C3H hostAfter introducing Fv-4^r gene using SFFV vector system, C3H bone marrow cells were transplanted to supralethally irradiated C3H host to create bone marrow chimeras (Fv-4^r-G3H * C3H). Fv-4^r gene product was expressed on the cell surface of hematopoietic cells in these chimera mice. The intensity of expression varied from mouse to mouse most of which expressed ranging from 10% to 20% of the expression by the hematopoietic cells of genetically Fv-4^r-bearing C4W mouse.2) Development of gene induction system with high efficiencyBy selecting vector systems and culture conditions, we could generate Fv-4^r-C3H * C3H chimeras that exhibited Fv-4^r expression of more than 30% of C4W mouse.3) Trial experiment to test the resistance of these chimeras to FLV-infectionA few number of Fv-4^r-C3H * C3H chimeras with high expression of Fv-4^r (>30% of C4W) exhibited resistance against FLV inoculation of 1x103 PFU.However, all mice died after infection with lx 104 PFU of FLV.By using Fr-4^r-G3H * C3H chimeras with high expression of Fv-4^r which were successfully conducted in the latest experiments, we would be able to develop a better model system for retrovirus-induced disease.