Basic studies In viral gene expression have provided insight into mechanisms of viral replication and paradigms for the delivery of recombinant genes with therapeutic potential. Beginning with analyses of the molecular regulation of HIV by a cellular transcription factor, NF-kB, our laboratories have defined molecular mechanisms of viral pathogenesis and begun to utilize gene transfer to develop molecular genetic approaches to the study and treatment of human disease. Based on these studies, different vectors and delivery systems have been developed to facilitate the delivery of recombinant genes to specific sites in vivo. For site-specific delivery, catheter-based gene transfer has been developed. Several gene products have been analyzed in cardiovascular and cancer models, including products which inhibit cell proliferation such as the p21 cyclin dependent kinase inhibitor and herpesvirus thymidine kinase, which show promise in restenosis models. These studies also provide insight into mechanisms of vascular proliferative diseases. Site-specific gene transfer has also been applied to human cancer. Immunotherapy of malignancy using an allogeneic class I MHC gene in human melanoma has been performed. Studies to date suggest that gene expression can be achieved without adverse effects, and that immune reactivity to melanoma can be enhanced and affect tumor growth in some cases. We are also studying methods to assess gene therapy for AIDS by inhibiting HIV replication in CD4 + cells. We have evaluated the ability of a tramdominant mutant protein, Rev MIO, to prolong T cell survival in HIV-infected individuals. These studies demonstrate that site-specific gene expression can be achieved by cell-mediated and direct gene transfer in vivo and applied to the treatment of several human diseases, including atherosclerosis, cancer and AIDS.
|Original language||English (US)|
|State||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology