INHIBITION OF REPLICATION OF HIV-1 BY RETROVIRAL VECTORS EXPRESSING TAT-ANTISENSE AND ANTI-TAT RIBOZYME RNA

A ribozyme was constructed that specifically cleaves RNA that contains the first coding exon of the tat gene of HIV-1. This anti-tat ribozyme was incorporated into a Moloney murine leukemia virus vector. A sequence containing only the 48-nucleotide antisense region of the ribozyme was also inserted into the retroviral vector. Human T-cell lines constitutively producing the tat-antisense and the anti-tat ribozyme RNA were created by transduction into Jurkat cells. When challenged with HIV-1, both the tat-antisense and anti-tat ribozyme-producing cells inhibited the replication of HIV-1. The antisense vector conferred a greater resistance to HIV-1 replication than did the anti-tat ribozyme vector. © 1992.