Journal ArticleDOI
Locked Nucleic Acid (LNA) Recognition of RNA: NMR Solution Structures of LNA:RNA Hybrids
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TLDR
It is suggested that the change in electronic density at the brim of the minor groove, introduced by the LNA modification, is causing an alteration of the pseudorotational profile of the 3'-flanking nucleotide, thus shifting this sugar equilibrium toward N-type conformation.Abstract:
Locked nucleic acids (LNAs) containing one or more 2‘-O,4‘-C-methylene-linked bicyclic ribonucleoside monomers possess a number of the prerequisites of an effective antisense oligonucleotide, e.g. ...read more
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RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform
C. Frank Bennett,Eric E. Swayze +1 more
TL;DR: The molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligon nucleotides behave in the body are focused on.
Journal ArticleDOI
Therapeutic targeting of microRNAs: current status and future challenges
Zhonghan Li,Tariq M. Rana +1 more
TL;DR: Current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides is summarized, various in vivo delivery strategies are discussed and ongoing challenges to ensure the specificity and efficacy of therapeutic oligon nucleotides in vivo are analysed.
Journal ArticleDOI
Sensitive and specific detection of microRNAs by northern blot analysis using LNA-modified oligonucleotide probes
TL;DR: The sensitivity in detecting mature microRNAs by northern blots was increased by at least 10-fold compared to DNA probes, while simultaneously being highly specific, as demonstrated by the use of different single and double mismatched LNA probes.
Journal ArticleDOI
LNA (Locked Nucleic Acid): High-Affinity Targeting of Complementary RNA and DNA†
Birte Vester,Jesper Wengel +1 more
TL;DR: The wide applicability of LNA oligonucleotides for gene silencing and their use for research and diagnostic purposes are documented in a number of recent reports, some of which are described herein.
Journal ArticleDOI
LNA: a versatile tool for therapeutics and genomics
TL;DR: Several reports have revealed LNA as a most promising molecule for the development of oligonucleotide-based therapeutics, including high capturing efficiencies and unambiguous scoring of single-nucleotide polymorphisms.
References
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Journal ArticleDOI
α-l-ribo-Configured Locked Nucleic Acid (α-L-LNA): Synthesis and Properties
Mads D. Sørensen,Lisbet Kværnø,Torsten Bryld,Anders E. Håkansson,Birgit Verbeure,G. Gaubert,Piet Herdewijn,Jesper Wengel +7 more
TL;DR: Binding studies revealed very efficient recognition of single-stranded DNA and RNA target oligonucleotide strands and stereoirregular α-L-LNA 11-mers containing a mixture of α- L-Lna monomers and DNA monomers were shown to display ΔTm values of +1 to +3 °C per modification toward DNA and +4 to +5 °C toward RNA when compared with the corresponding unmodified DNA·DNA and DNA·RNA reference duplexes.
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Relaxation matrix analysis of 2D NMR data
TL;DR: In this article, the authors survey some of the approaches taken to derive structural information from the 2D NOE experiment and present guidelines for obtaining the most accurate and realistic structural parameters from the spectral data.
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Novel convenient syntheses of LNA [2.2.1]bicyclo nucleosides
TL;DR: In this article, a robust linear approach allowing selective formation of the desired [2.2.1]bicyclo LNA nucleosides via a tricyclic nucleoside intermediate is introduced.
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Oligonucleotide N3'-->P5' phosphoramidates as potential therapeutic agents.
TL;DR: Experimental results indicate that oligonucleotide phosphoramidates can be used as efficient and specific modulators of gene expression by an antigene mechanism of action and structurally mimic native RNA complexes, which could be efficiently and specifically recognized by the RNA binding proteins, such as HIV-1 Rev and Tat.
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Structure and dynamics of a DNA.RNA hybrid duplex with a chiral phosphorothioate moiety: NMR and molecular dynamics with conventional and time-averaged restraints.
TL;DR: Intermediate E sugar puckers are artifacts produced by the attempt to fit all the structural constraints simultaneously when in reality more than one conformer is present, and they only appear in a very low population in the MD-tar ensemble.