Document Detail


Locked vs. unlocked nucleic acids (LNA vs. UNA): contrasting structures work towards common therapeutic goals.
MedLine Citation:
PMID:  21556437     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Oligonucleotide chemistry has been developed greatly over the past three decades, with many advances in increasing nuclease resistance, enhancing duplex stability and assisting with cellular uptake. Locked nucleic acid (LNA) is a structurally rigid modification that increases the binding affinity of a modified-oligonucleotide. In contrast, unlocked nucleic acid (UNA) is a highly flexible modification, which can be used to modulate duplex characteristics. In this tutorial review, we will compare the synthetic routes to both of these modifications, contrast the structural features, examine the hybridization properties of LNA and UNA modified duplexes, and discuss how they have been applied within biotechnology and drug research. LNA has found widespread use in antisense oligonucleotide technology, where it can stabilize interactions with target RNA and protect from cellular nucleases. The newly emerging field of siRNAs has made use of LNA and, recently, also UNA. These modifications are able to increase double-stranded RNA stability in serum and decrease off-target effects seen with conventional siRNAs. LNA and UNA are also emerging as versatile modifications for aptamers. Their application to known aptamer structures has opened up the possibility of future selection of LNA-modified aptamers. Each of these oligonucleotide technologies has the potential to become a new type of therapy to treat a wide variety of diseases, and LNA and UNA will no doubt play a part in future developments of therapeutic and diagnostic oligonucleotides.
Authors:
Meghan A Campbell; Jesper Wengel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-10
Journal Detail:
Title:  Chemical Society reviews     Volume:  -     ISSN:  1460-4744     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0335405     Medline TA:  Chem Soc Rev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Nucleic Acid Center, Institute for Physics and Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. jwe@ifk.sdu.dk.
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