An RNA modification with remarkable resistance to RNase A

Abstract

A 3'-deoxy-3'-C-methylenephosphonate modified diribonucleotide is highly resistant to degradation by spleen phosphodiesterase and not cleaved at all by snake venom phosphodiesterase. The most remarkable finding is that, despite the fact that both the vicinal 2-hydroxy nucleophile and the 5'-oxyanion leaving group are intact, the 3'-methylenephosponate RNA modification is also highly resistant towards the action of RNase A.

Modified internucleoside linkages for nuclease-resistant oligonucleotides

“…[29][30][31][32][33][34][35][36] However, it is essential that the nuclease resistance of any newly synthesised backbone-, ribose-, or base-modification has to be evaluated before considering therapeutic or biotechnological applications. [37][38][39][40] The discovery that an ODN is able to inhibit in cellulo viral replication dates back to 1978. 41 After 20 years of research the first antisense oligonucleotide (ODN-AS) was commercialized in 1998 against cytomegalovirus retinitis (Fomivirsen, commercialized as Vitravene s ).…”