This project serves as the antiviral evaluation laboratory for our Drug Discovery Group. The laboratory will characterize specific and nonspecific effects of anti-HIV-1 RNA using HIV-1 and control HIV-2 and will compare viral protein expression, DNA integration, in vivo cleavage HIV RNA, and generation of infectious virus. In conjunction with Projects 1 and 4, the laboratory will evaluate the antiviral activity and stability of endogenously expressed antiviral RNA, particularly ribozymes, in cell lines transformed with plasmid or retrovirus vectors. The anti-HIV-1 effects of retrovirus-transduced ribozyme expression in hematopoietic cells will be explored. To evaluate the antiviral potency of synthetic ribozyme, the laboratory will compare both chemically and enzymatically manufactured materials developed at United States Biochemical Corporation and will correlate enzyme kinetic and biostability studies of Projects 1 and 2 with functional antiviral activity. Finally, to characterize the potential limitations of antiviral RNA, the laboratory will determine the effect of ribozyme on non-targeted cellular RNA and on the occurence of viral resistance in long term cultures. The overall goals of this project will be to establish and evaluate optimal methods of HIV inhibition using ribozyme and other antiviral RNA to determine if this can become a candidate method for the treatment of AIDS.
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