We describe the synthesis of 2′-O-methyl, 2′-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as Inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2′-O-modifled compounds were designed to possess the binding affinity of an RNA molecule towards a complementary RNA target with an enhanced stability against nucleases. The 2′-O-methyl and 2′-O-ethyl antisense compounds function as potent inhibitors of the reaction at 1–10 nM, approximately 5-fold more effective than a natural antisense RNA molecule and requiring an approximate 5-fold excess over the target RNA for 80% inhibition of the processing reaction.