Design of hammerhead ribozymes to distinguish single base changes in substrate RNA

Hammerhead ribozymes are attractive tools in antisense gene inactivation because of their catalytic cleavage of target molecules. High sequence discrimination should be possible, since the cleavage efficiencies were already significantly reduced, if single base changes in substrate RNA introduce mismatches next to the cleavage site. This was observed at the first innermost base pair in helix I and the two innermost base pairs in helix III. In addition to its position, the nature of the mismatch pair was important.