Of all the catalytic RNAs the hammerhead ribozyme is the most chemical
ly modified and structurally studied. Such studies have resulted in im
provements in the nuclease resistance of ribozymes, reductions in thei
r size, and improvements in their catalytic efficiency. These improvem
ents have facilitated the use of ribozymes for therapeutic application
s, and have allowed us to study how the three-dimensional structure of
the enzyme and its array of functional groups interact to create a ca
talytic site where a phosphodiester bond is cleaved.