Discrimination between ribonuclease H- and ribonuclease L-mediated RNA degradation by 2′- O-methylated 2-5A-antisense oligonucleotides

2′,5′-Oligoadenylate (2-5A) antisense chimeric oligonucleotides were synthesized containing varying 2′- O-methyl-ribonucleotide substitution patterns in the antisense domain. The ability of these composite oligonucleotides to mediate RNase H- and RNase L-catalyzed RNA degradation showed that these two enzymes have different activation requirements. 2′,5′-Oligoadenylate antisense oligonucleotides varying 2′-O-methyl-ribonucleotide substitution patterns in the antisense domain were synthesized and evaluated for their ability to mediate RNase H- and RNase L-catalyzed RNA degradation.