Ribozymes that cleave an RNA sequence from human immunodeficiency virus: the effect of flanking sequence on rate

Ribozymes designed to cleave sequences specific to viral RNA may be better antiviral agents than simple antisense oligonucleotides. High catalytic activity with the lowest possible chain length is desired for this purpose. We have synthesized several hammerhead ribozymes that cleave sequences from HIV-1 RNA. On reducing from 20 to 12 the base pairs formed with the substrate, the rate of cleavage at 37 degrees C increased 10-fold. Deletions from the stem/loop structure in the ribozyme also increased the initial rate of reaction.