Novel ribozyme, RNA decoy, and siRNA approaches to inhibition of HIV in a gene therapy setting

Abstract At present, treatment for human immunodeficiency virus (HIV)-1 infection employs highly active anti-retroviral therapy (HAART), which utilizes a combination of retroviral therapy (RT) and protease inhibitors [1] . Unfortunately, HIV can escape many therapies because of its high mutation rate and the complexity of its pathogenesis. HIV-1 integrates into the cellular genome, which facilitates persistence and acts as a reservoir for reactivation and replication. As an alternative or adjuvant to chemotherapy we have been developing a ribonucleic acid (RNA) based gene therapy approach for the treatment of HIV-1 infection. Dr. Narva Sarver was a visionary and an activist who saw the potential for gene therapy as a long term treatment for HIV-1 infection [2] . She was a strong proponent of RNA based gene therapy, in particular ribozyme gene therapy for HIV-1 treatment. Working in close communication with Dr. Sarver over the past several years we have investigated gene therapy approaches that employ the use of anti-HIV ribozymes to control viral replication in acquired immunodeficiency syndrome (AIDS) patients. This article summarizes our past work, as well as describing new technologies being developed for application in a gene therapy setting.