Ribozyme-Mediated Repair of Mutant p53 Transcripts in Breast Cancer Cells

This project explores the potential of a new and innovative approach to human gene therapy that may prove to be useful for the treatment or prevention of a range of genetic diseases including many types of cancer. We have previously demonstrated that a trans-splicing group I ribozyme can be employed to repair mutant transcripts in E. coli and mammalian cells. Ribozyme-mediated repair of mutant mRNAs associated with a range of human diseases is now experimentally tractable. In this study we have begun to explore the potential of this process for the repair of mutant transcripts implicated in the development and progression of breast cancer. Because mutation of the p53 gene is the most common genetic change seen in a wide variety of malignancies including breast cancer, we have initially focused upon the repair of mutant p53 transcripts. Toward this end, we have developed ribozymes that can react with mutant p53 RNAs in breast cancer cell lines and are now in the process of determining if the ribozymes can repair these mutant RNAs and revert the neoplastic phenotype of these cells.