The overall goal of this project is to determine whether anti-sense RNA introduced with retroviral vectors can block the replication of HIV in appropriate host cells. There are three specific aims: 1) Prepare and test alternative retroviral vectors for their ability to express high levels of anti-sense HIV RNA in human T-cells and other relevant lineages; 2) Test the ability of anti-sense RNA to protect these various cells from infection with HIV in culture; 3) To exploit an avian retrovirus model, in which the anti-sense RNA block to viral replication has already been shown to be effective, to test whether retrovirus expressed anti-sense RNA can be introduced into lymphoid stem cells and whether the progeny of such cells are protected from retroviral infection in whole animals. These experiments are envisioned as providing a basis for planning of preclinical test of the effects of anti-sense RNA expression on development of disease in-vivo. These experiments will determine the optimal fragment of the HIV genome to use for inhibiting replication; the stage of the viral life cycle interupted by anti-sense RNA, the ability of anti-sense RNA to inhibit viral replication in macrophage and glial lineage cells and in peripheral blood cells as well as in prototypic T-cell lines.

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Fred Hutchinson Cancer Research Center
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