ArticleNucleic acids research2010
Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 245 citations in OpenAlex.
- An Enzymatic Platform for Late-Stage (Radio)isotope Labelling of Oligonucleotides With Methyltransferases.Angewandte Chemie (International ed. in English) · 2026Article
- Development of ARL4C antisense oligonucleotide with reduced off-target effects and enhanced efficacy as an anti-cancer drug.In vitro cellular & developmental biology. Animal · 2026Article
- Selective blockade of microRNA-31-5p/calcitonin receptor interaction reverses established atrial fibrosis and atrial arrhythmia substrate.Research square · 2026Article
- Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis.Cell death discovery · 2025Review
- Restoring chloride efflux in cystic fibrosis with TMEM16a antisense oligonucleotides.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The impact of dietary salt on the development of hypertension and gut microbiome dysbiosis in captive-bred vervet monkeys (Chlorocebus aethiops).BMC veterinary research · 2025Article
- Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides.Royal Society open science · 2025Article
- miR-200c inhibition and catalase accelerate diabetic wound healing.Journal of biomedical science · 2025Article
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Antisense Oligonucleotide STK-002 Increases OPA1 in Retina and Improves Mitochondrial Function in Autosomal Dominant Optic Atrophy Cells.Nucleic acid therapeutics · 2024Article
- Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2024Article
- Development of the 12-Base Short Dimeric Myogenetic Oligodeoxynucleotide That Induces Myogenic Differentiation.Biotech (Basel (Switzerland)) · 2024Article
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Evaluation of Chemically Modified Nucleic Acid Analogues for Splice Switching Application.ACS omega · 2023Review
- Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry.Nature communications · 2023Article
- An enhanced biophysical screening strategy to investigate the affinity of ASOs for their target RNA.RSC chemical biology · 2023Article
- Synthesis of P-Modified DNA from Boranophosphate DNA as a Precursor via Acyl Phosphite Intermediates.The Journal of organic chemistry · 2023Article
- Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer.Biomedicines · 2023Article
- Investigation of Sequence-Penetration Relationships of Antisense Oligonucleotides.Chembiochem : a European journal of chemical biology · 2023Article
- LNA blockers for improved amplification selectivity.Scientific reports · 2023Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 potency both in vitro and in vivo compared to longer oligonucleotides. The short LNA oligonucleotides were more target specific, and they exhibited the same biodistribution and tissue half-life as longer oligonucleotides. Pharmacology studies in both mice and non-human primates were conducted with a 13-mer LNA oligonucleotide against apoB, and the data showed that repeated dosing of the 13-mer at 1-2 mg/kg/week was sufficient to provide a significant and long lasting lowering of non-high-density lipoprotein (non-HDL) cholesterol without increasing serum liver toxicity markers. The data presented here show that oligonucleotide length as a parameter needs to be considered in the design of antisense oligonucleotide and that potent short oligonucleotides with sufficient target affinity can be generated using the LNA chemistry. Conclusively, we present a 13-mer LNA oligonucleotide with therapeutic potential that produce beneficial cholesterol lowering effect in non-human primates.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.