Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

Figure 5

Chemical modifications of miRNA-targeting modulators. Anti-miR oligonucleotides have been chemically modified in order to achieve better stability against serum nucleases and to increase the binding affinity to targeted miRNAs. Most of the modifications are at the 2′ position of the sugar moiety, as 2′-O-methyl (2′-OMe), 2′-O-methoxyethyl (2′-MOE), and 2′-fluoro (2′-F). Locked nucleic acid (LNA) is a bicyclic RNA analogue in which ribose is locked by introduction of a methylene bridge between the 2′ oxygen and the 4′ carbon of the pentose. In addition, most anti-miR oligonucleotides contain phosphorothioate backbone linkages in which sulfur replaces one of the nonbridging oxygen atoms in the phosphate group. Morpholino oligomers replace the ribose with a methylenemorpholine ring (to which bases are attached) with phosphorodiamidate linkages. PNA oligomers are oligonucleotide analogues in which the ribose-phosphate backbone has been replaced with a peptide-like structure containing N-(2-aminoethyl)-glycine units. Both morpholino and PNA oligomers are uncharged, which facilitates the interaction with targeted miRNAs.