The hammerhead ribozyme motif can be engineered to function as a sequence-specific endoribonuclease for use as a specific inhibitor of gene expression (1 ,2 ). However, efficient inhibition often requires high ribozyme concentrations and a large excess of ribozyme over substrate (3 ). Moreover, the extent of inhibition seen with an inactive ribozyme mutant is often on the same order of magnitude as for the active version owing to antisense effects (4 ). Thus far, it appears that in vivo applications of ribozymes have not taken full advantage of their demonstrated in vitro potential.
