Figure 1. Drug-like chemical modifications to nucleic acids. Nucleic acids are not drug-like molecules, and chemical modifications are required to improve their pharmacokinetic and other properties before they can be used as therapeutics. Several examples are illustrated. (I) Locked nucleic acids (LNAs) are modified nucleotides with an additional bond between the 2'-oxygen and 4'-carbon of the ribose sugar. Santaris Pharma A/S owns the rights to the therapeutic application of these molecules. (II) Modifications to the phosphodiester backbone include phosphorothioate (PS) or phosphorodiamidate linkages. PS linkages are part of Isis Pharmaceutical Inc.'s first-generation chemistry, and phosphorodiamidate morpholino oligonucleotides (PMOs) were developed by Sarepta Therapeutics Inc. (III) 2'-O-methoxyethyl, Isis' second-generation chemistry, or 2'-O-Me, in Silence Therapeutics plc's AtuRNAis, are also modifications to the ribose sugar.