Locked Nucleic Acid Gapmers and Conjugates Potently Silence ADAM33, an Asthma-Associated Metalloprotease with Nuclear-Localized mRNA

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Locked Nucleic Acid Gapmers and Conjugates Potently Silence ADAM33, an Asthma-Associated Metalloprotease with Nuclear-Localized mRNA

Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely, the antisense approach that recruits RNase H to cleave target RNA and the RNAi approach that recruits the RISC complex to cleave target RNA. Multiple chemical designs can be used to elicit each pathway. We compare the silencing of the asthma susceptibility gene ADAM33 in MRC-5 lung fibroblasts using ...

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Locked Nucleic Acid gapmers and conjugates induce potent silencing of ADAM33, an asthma-associated metalloprotease with nuclear-localized mRNA

Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely the antisense approach that recruits RNase H to cleave target RNA and the RNA interference (RNAi) approach that recruits the RISC complex to cleave target RNA. Multiple chemical designs can be used to elicit each pathway. We now compare the silencing of the asthma susceptibility gene ADAM33 in MRC-5 l...

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Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates

The potency and specificity of locked nucleic acid (LNA) antisense oligonucleotides was investigated as a function of length and affinity. The oligonucleotides were designed to target apolipoprotein B (apoB) and were investigated both in vitro and in vivo. The high affinity of LNA enabled the design of short antisense oligonucleotides (12- to 13-mers) that possessed high affinity and increased ...

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Locked nucleic acid molecular beacons.

A novel LNA-MB (molecular beacon based on locked nucleic acid bases) has been designed and investigated. It exhibits very high melting temperature and is thermally stable, shows superior single base mismatch discrimination capability, and is stable against digestion by nuclease and has no binding with single-stranded DNA binding proteins. The LNA-MB will be widely useful in a variety of areas, ...

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ژورنال

عنوان ژورنال: Molecular Therapy - Nucleic Acids

سال: 2017

ISSN: 2162-2531

DOI: 10.1016/j.omtn.2017.06.012