Inhibition of Gene Expression by Ribozymes

RNA enzymes, or ribozymes, can be defined as RNA molecules that promote a variety of reactions involving RNA and DNA molecules. These include site-specific cleavage, ligation, polymerization, and phosphoryl exchange (1 ). The use of ribozymes for medical therapy was recognized soon after RNA catalysis was discovered in the early 1980s (2 ). Three broad classes, naturally occurring ribozymes have been recognized: (1 ) RNase P, required for tRNA processing; (2 ) self-splicing introns, including group I and II introns of bacteria, mitochondria, and chloroplasts; and (3 ) selfcleaving viral agents, including hepatitis delta virus and components of plant viroids that cleave the RNA genome during replication. Because of their small size and great specificity, the self-cleaving ribozymes have the greatest potential for medical applications. The ability of these ribozymes to cleave other RNA molecules at specific sites makes them useful as inhibitors of viral replication or of cell proliferation (3 -8 ).