THERAPEUTIC APPLICATIONS OF RIBOZYMES

The demonstration that RNA can be cleaved by cis or trans ribozymes (c atalytic RNAs, RNA enzymes) has potentially important therapeutic impl ications. Since their discovery in the 1980s, the biochemistry and con served sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expression because of their simple st ructure, site-specific cleavage activity, and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional targ et sites for ribozymes are in initial phases of development and design . Ribozymes have been targeted against a myriad of genes, including on cogenes (ras, BCR-ABL, c-fos) and drug resistance genes, as well as th e human immunodeficiency virus-type 1 genome. These ribozymes have cle aved the target RNAs in vitro and altered the cellular pathology. Curr ently, the therapeutic application of ribozymes to human diseases is l imited by gene transfer systems. It is anticipated that ribozymes ulti mately will play an important role in human gene therapy.