The Development and Assessment of a Therapeutic Strategy for Myotonic Dystrophy

We have developed a biomolecu1e (ribozyme) that can potentially remove mutations from the genetic material (RNA) of patients with a variety of genetic diseases. In this grant, we sought to understand exactly how this ribozyme works, with the ultimate goal of exploiting this information for developing a ribozyme that can specifically remove the mutation that causes Myotonic Dystrophy. This past year we have made dramatic progress towards this goal. We have shown that we can develop such ribozymes, that we can engineer them to target the Myotonic Dystrophy mutation (initially in a cell free system), and that the process is reasonably specific. In addition, we have learned a great deal about how this reaction works, including understanding the catalytic mechanism, understanding how the ribozyme binds its target, and how we can modify the ribozyme to specifically and effectively excise the Myotonic Dystrophy mutation. We have laid a solid foundation of understanding that we are now exploiting for developing