2'-O-METHYL, 2'-O-ETHYL OLIGORIBONUCLEOTIDES AND PHOSPHOROTHIOATE OLIGODEOXYRIBONUCLEOTIDES AS INHIBITORS OF THE INVITRO U7 SNRNP-DEPENDENT MESSENGER-RNA PROCESSING EVENT

We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxy-ribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified 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.