Following the discovery of catalytic RNA ( 1 ), a number of different ribozymes have been found. Most ribozymes carry out site-specific cleavage of the RNA phosphodiester backbone, although important exceptions may be emerging ( 2 , 3 ). The catalytic center and reaction site of several naturally occurring self-cleaving molecules have been dissected, and used to develop ribozymes that cleave external substrates ( 4 ). Because RNA structure is responsible for both catalytic activity and substrate recognition, ribozymes may be engineered to direct the inactivation of targeted cellular and viral RNAs through a catalytic cleavage mechanism ( 5 ). These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.