Locked nucleic acids (LNA) and medical applications

Ørum, Henrik; Wolter, Andreas; Kongsbak, Lars

doi:10.1007/bf02484567

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…The enhanced stability of LNA-containing materials, combined with low toxicity and uncomplicated synthesis and processing, has triggered their industrial-scale production. A multitude of bioapplications of LNA materials has recently been reported . These include usage of LNA assemblies as PCR primers and agents affecting RNase H activity , as well as applications as LNAzymes, and in antisense and antigene therapeutics. , Also, LNA has been proposed to be used in diagnostics via microarrays targeting RNA …”

Section: Introductionmentioning

confidence: 99%

The Structure of LNA:DNA Hybrids from Molecular Dynamics Simulations: The Effect of Locked Nucleotides

Ivanova

Rösch

2007

J. Phys. Chem. A

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Locked nucleic acids (LNAs) exhibit a modified sugar fragment that is restrained to the C3'-endo conformation. LNA-containing duplexes are rather stable and have a more rigid structure than DNA duplexes, with a propensity for A-conformation of the double helix. To gain detailed insight into the local structure of LNA-modified DNA oligomers (as a foundation for subsequent exploration of the electron-transfer capabilities of such modified duplexes), we carried out molecular dynamics simulations on a set of LNA:DNA 9-mer duplexes and analyzed the resulting structures in terms of base step parameters and the conformations of the sugar residues. The perturbation introduced by a single locked nucleotide was found to be fairly localized, extending mostly to the first neighboring base pairs; such duplexes featured a B-type helix. With increasing degree of LNA modification the structure gradually changed; the duplex with one complete LNA strand assumed a typical A-DNA structure. The relative populations of the sugar conformations agreed very well with NMR data, lending credibility to the validity of the computational protocol.

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Section: Introductionmentioning

confidence: 99%

The Structure of LNA:DNA Hybrids from Molecular Dynamics Simulations: The Effect of Locked Nucleotides

Ivanova

Rösch

2007

J. Phys. Chem. A

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“…2B ) [ 43, 44 ]. Third generation ASO modifications include phosphorodiamidate morpholinos (PMOs), peptide nucleic acids (PNAs), and tricyclo-DNAs [ 43, 44 ] as well as ethylene-bridged nucleic acids (ENAs) and locked nucleic acids (LNAs), a class of nucleic acid analogues with a methylene bridge connecting the ribose 2’-oxygen and 4’-carbon [ 45 ] ( Fig. 2C ).…”

Section: Oligonucleotide Chemistry For Treatment Of Rare Diseasesmentioning

confidence: 99%

Emerging Oligonucleotide Therapeutics for Rare Neuromuscular Diseases

Aoki

Wood

2021

JND

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Research and drug development concerning rare diseases are at the cutting edge of scientific technology. To date, over 7,000 rare diseases have been identified. Despite their individual rarity, 1 in 10 individuals worldwide is affected by a rare condition. For the majority of these diseases, there is no treatment, much less cure; therefore, there is an urgent need for new therapies to extend and improve quality of life for persons who suffer from them. Here we focus specifically on rare neuromuscular diseases. Currently, genetic medicines using short antisense oligonucleotides (ASO) or small interfering ribonucleic acids that target RNA transcripts are achieving spectacular success in treating these diseases. For Duchenne muscular dystrophy (DMD), the state-of-the-art is an exon skipping therapy using an antisense oligonucleotide, which is prototypical of advanced precision medicines. Very recently, golodirsen and viltolarsen, for treatment of DMD patients amenable to skipping exon 53, have been approved by regulatory agencies in the USA and Japan, respectively. Here, we review scientific and clinical progress in developing new oligonucleotide therapeutics for selected rare neuromuscular diseases, discussing their efficacy and limitations.

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“…LNAs have found applications in material science, molecular diagnostics and biotechnology, while addressing challenges such as target binding selectivity as well as contributing to enzymatic and chemical stability. 192,193 The synthesis of LNA and a wide range of LNA applications and their use as therapeutics has been covered in multiple reviews. 186,[192][193][194][195] Despite the obvious beneficial properties of LNA, the full potential of LNAs in the programmable assembly of nanoparticles remains largely underexplored.…”

Section: Locked Nucleic Acidsmentioning

confidence: 99%

“…192,193 The synthesis of LNA and a wide range of LNA applications and their use as therapeutics has been covered in multiple reviews. 186,[192][193][194][195] Despite the obvious beneficial properties of LNA, the full potential of LNAs in the programmable assembly of nanoparticles remains largely underexplored. In the following section we will describe the current state of the art.…”

Section: Locked Nucleic Acidsmentioning

confidence: 99%