“…As a result, phosphorothioate oligos remain the most widely used base analogue, and are currently being tested in a number of clinical trials (Roth and Cristiano, 1997;Wagner and Flanagan, 1997). Second generation oligonucleotides include: substituting pyrimidines at the C-5 position with 5-methyl, 5-bromo and 5-propynyluracil (Lonnberg and Vuorio, 1996) replacement of the sugar and phosphate residues with alkylamide or carbamate linkage (Crooke and Bennett, 1996;Stirchak et al, 1989); 2 -O-propyl, 2 -methoxyethoxy, 2 -O-methyl, 2 -O-allyl and 2 -fluoro ribose modifications (Monia et al, 1993;Wagner, 1995;Crooke and Bennett, 1996); covalent linkage of functional groups, such as cholesterol, to alter physical properties, provide ligands or provide resistance (Krieg et al, 1993;Manoharan et al, 1995;Crooke and Bennett, 1996); replacement of the central phosphorus with a methylene group creating a formacetal linkage (Milligan et al, 1994). All of these modifications display either enhanced affinity or resistance or both, but many of them do not elicit RNase H activity.…”