The long-term commercial objective is to deliver therapeutic genes in vivo. Retroviral vectors provide an efficient method for gene transfer in eukaryotic cells. Current retroviral vectors used in human gene therapy trials are derived from murine leukemia virus, which requires a dividing host cell for completion of virus life cycle. When murine retroviral vectors are used to infect the resting cells, the nuclear localization of viral pre-integration complex is arrested in the cytoplasma. In contrast, establishment of an integrated provirus after infection by the lentivirus (i.e. HIV-1 and SIV) is independent of host cell proliferation. Retrovirus becomes an attractive candidate for gene transfer vector because of its ability to replicate in non-dividing cells (i.e., monocyte, tissue macrophage, follicular dendritic cells, and microglial cells). Based on these properties of lentivirus, we propose to develop retroviral vectors, which will either deliver foreign genes and/or establish gene expression in non-dividing cells. For safety reasons, the structural protein genes of SIV will be used to construct a lentiviral vector for gene transfer in primary cells. The gene transfer system developed in this proposal should facilitate further development of therapeutic gene transfer in vivo.
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