Hairpin Ribozyme Gene Therapy for the Treatment of HIV 1

Ribozyme (Rz) gene therapy has emerged as a powerful approach towards inhibition of virus infectionterm objective is to develop hairpin Rz gene therapy in combination with other approaches for the trinfection and AIDS. We have recently defined a double hairpin ribozyme vector which, when introducedresults in effective resistance to HIV-1 infection. To facilitate the transition of this laboratoryapplication, we will critically evaluate this promising vector in a system using peripheral blood lyclinical isolates, prior to initiation of a phase l clinical trial. In a continuous effort to identiovercome the potential problem of viral resistance, we have now proposed a unique approach to mobiliin conjunction with the hairpin ribozyme to attack the virus. We will turn a single hairpin ribozymemolecule that directs two separate RNase activities against a single substrate RNA. Resistant mutantaltered cleavage sites critical to the hairpin ribozyme activity would, in this approach, remain senribozyme and vise versa.