Abstract
Primer extension arrest (PEA) studies have demonstrated that antisense oligonucleotides (ß112C, ß114C), which lie upstream of a ribozyme targeted to ß‐amyloid peptide precursor (ßAPP) mRNA, but not sense oligonucleotides (ß112S, ß116S) or a scrambled oligonucleotide, ß116M, affect ribozyme‐mediated cleavage in vitro. Substrate dissociation experiments revealed that the ribozyme binding site in this mRNA was masked; PEA kinetics showed the association of the ribozyme and substrate was enhanced by antisense oligonucleotide binding. These studies suggest that masked ribozyme cleavage sites that may occur in disease‐causing mRNAs can be targeted for degradation using “facilitator” oligonucleotides.