Grant: Catalyst Grant: Pandemic Preparedness

The ability of ribozymes, RNA molecules that possess enzymatic activities, to specifically recognize and subsequently catalyze the cleavage of RNA substrates makes them attractive as therapeutic tools for the inactivation of viruses. Our goal is to use ribozymes to specifically cleave influenza RNA transcripts thereby inhibiting the replication of the virus. During the past year, we have designed various ribozymes aimed at inhibiting the replication of the virus, performed the basic in vitro experiments demonstrating the efficiency of influenza-specific ribozymes, developed a system to monitor the efficiency of ribozymes in human cells, and finally, initiated experiments in animal models to identify the most suitable system to deliver the selected ribozymes to target cells in the lungs. We now feel confident that we have all the necessary tools to assess the efficacy of our gene-inactivation approach against influenza. In the current proposal, we want to complete the screen our collection of ribozymes and ultimately monitor the ability of selected ribozymes to inhibit the replication of the virus in animals.