Locked Nucleic Acids (LNAs)

With few exceptions, experimental success in molecular biology is dependent upon specific, discriminating, and persistent hybridization events involving synthetic oligonucleotides and their complementary target sequences. While unmodified oligodeoxynucleotides will routinely form desired DNA:DNA and DNA:RNA duplexes, synthesis of various modifications that confer enhanced high-affinity recognition of DNA and RNA targets has been an ongoing endeavor. A variety of nucleic acid analogs have been developed that display increased thermal stabilities when hybridized to with complementary DNAs or RNAs as compared to unmodified DNA:DNA and DNA:RNA duplexes. Among these analogs are peptide nucleic acids (PNAs)(Hyrup and Neilson, 1996; Nielson and Haaima, 1997), 2’-fluoro N3-P5’-phosphoramidites (Schulz and Gryaznov, 1996), and 1’, 5’anhydrohexitol nucleic acids (HNAs)(VanAerschot et al., 1996; Hendrix et al., 1997). While such analogs succeed to varying degrees in achieving increased thermal stabilities, they fail to provide enhanced target recognition. A relatively benign modification that has demonstrated both of these desirable qualities is the Locked Nucleic Acid (LNA).