Structure of an LNA monomer

A locked nucleic acid (LNA), often referred to as inaccessible RNA, is a modified RNA nucleotide. The ribose moiety of an LNA nucleotide is modified with an extra bridge connecting the 2' and 4' carbons. The bridge "locks" the ribose in the 3'-endo structural conformation, which is often found in the A-form of DNA or RNA. LNA nucleotides can be mixed with DNA or RNA bases in the oligonucleotide whenever desired. Such oligomers are commercially available. The locked ribose conformation enhances base stacking and backbone pre-organization. This significantly increases the thermal stability (melting temperature) of oligonucleotides.^[1]

LNA nucleotides are used to increase the sensitivity and specificity of expression in DNA microarrays, FISH probes, real-time PCR probes and other molecular biology techniques based on oligonucleotides. For the in situ detection of miRNA the use of LNA is currently (2005) the only efficient method. A triplet of LNA nucleotides surrounding a single-base mismatch site maximizes LNA probe specificity unless the probe contains the guanine base of G-T mismatch.^[2]

A new hepatitis C drug based on a LNA targeting a microRNA is in clinical testing as of late 2009.^[3]

[edit] References

1. ^ Kaur, H; Arora, A; Wengel, J; Maiti, S (2006). "Thermodynamic, Counterion, and Hydration Effects for the Incorporation of Locked Nucleic Acid Nucleotides into DNA Duplexes". Biochemistry 45 (23): 7347–55. doi:10.1021/bi060307w. PMID 16752924. 
2. ^ You Y.; Moreira B.G.; Behlke M.A. and Owczarzy R. (2006). "Design of LNA probes that improve mismatch discrimination". Nucleic Acids Res. 34 (8): e60. doi:10.1093/nar/gkl175. PMID 16670427. http://nar.oxfordjournals.org/cgi/reprint/34/8/e60?ijkey=IqLeijzpwQHCzit&keytype=ref. 
3. ^ Emily Singer. (2009). "Hepatitis C Drug Targets RNA". Technology Review. http://www.technologyreview.com/biomedicine/24059/. 

[edit] External links

• LNA™ Oligo Tools and Design Guidelines
• LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA
• LNA: a versatile tool for therapeutics and genomics
• Alternative Nucleic Acid Analogues for Programmable Assembly: Hybridization of LNA to PNA
• Locked Nucleic Acid (LNA™) Technology