Inhibition of CCR5-dependent HIV-1 infection by hairpin ribozyme gene therapy against CC-chemokine receptor 5

CCR-5 is a major cellular coreceptor for R5 strains of HIV-1. Individuals c arrying a homozygous 32-base-pair deletion in this gene are apparently heal thy and are relatively resistant to HIV-1 infection. Since CCR5 appears to be dispensable for the host, but important for initial HIV-1 infection, CCR 5 mRNA is an excellent therapeutic target for inhibiting HIV-1 replication via ribozyme knockout. We report here that hairpin ribozymes are able to re duce cellular CCR5 mRNA and cell surface CCR5 when stably introduced into P M1 cells by transduction with recombinant adenoassociated viral vector. The ribozymes effectively protect the cells from infection by R5 HIV-1 strains or non-syncytium-inducing clinical isolates commensurate with a reduction in CCR5 mRNA. These results suggest a novel gene therapy approach to preven ting or slowing the disease progression of HIV-1 infection, (C) 2000 Academ ic Press.