ArticleNucleic acids research2012
TricycloDNA-modified oligo-2'-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues--a comparative study of oligonucleotide length, design and chemistry.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
44 citing papers in PubMed, 89 citations in OpenAlex.
- Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer.Journal for immunotherapy of cancer · 2022Trial
- LINC01235 Is an Upstream Regulator of the NFIB Gene and the Notch Pathway in Triple-Negative Breast Cancer.Molecular cancer research : MCR · 2025Article
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Antisense oligonucleotides and their applications in rare neurological diseases.Frontiers in neuroscience · 2024Review
- Development of 8-17 XNAzymes that are functional in cells.Chemical science · 2023Article
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- Article
- Targeting Smyd3 by next-generation antisense oligonucleotides suppresses liver tumor growth.iScience · 2021Article
- Docosanoic acid conjugation to siRNA enables functional and safe delivery to skeletal and cardiac muscles.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Site-specific incorporation of 5'-methyl DNA enhances the therapeutic profile of gapmer ASOs.Nucleic acids research · 2021Article
- Efficient Gene Suppression by DNA/DNA Double-Stranded Oligonucleotide In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression.Nature communications · 2020Article
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance.Journal of lipid research · 2020Article
- Identifying and Avoiding tcDNA-ASO Sequence-Specific Toxicity for the Development of DMD Exon 51 Skipping Therapy.Molecular therapy. Nucleic acids · 2020Article
- Targeting murine alveolar macrophages by the intratracheal administration of locked nucleic acid containing antisense oligonucleotides.Drug delivery · 2019Article
- Conjugation of hydrophobic moieties enhances potency of antisense oligonucleotides in the muscle of rodents and non-human primates.Nucleic acids research · 2019Article
- Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines.Nucleic acids research · 2019Article
- Characterization of the interactions of chemically-modified therapeutic nucleic acids with plasma proteins using a fluorescence polarization assay.Nucleic acids research · 2019Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the evaluation of 20-, 18-, 16- and 14-mer phosphorothioate (PS)-modified tricycloDNA (tcDNA) gapmer antisense oligonucleotides (ASOs) in T(m), cell culture and animal experiments and compare them to their gap-matched 20-mer 2'-O-methoxyethyl (MOE) and 14-mer 2',4'-constrained ethyl (cEt) counterparts. The sequence-matched 20-mer tcDNA and MOE ASOs showed similar T(m) and activity in cell culture under free-uptake and cationic lipid-mediated transfection conditions, while the 18-, 16- and 14-mer tcDNA ASOs were moderate to significantly less active. These observations were recapitulated in the animal experiments where the 20-mer tcDNA ASO formulated in saline showed excellent activity (ED(50) 3.9 mg/kg) for reducing SR-B1 mRNA in liver. The tcDNA 20-mer ASO also showed better activity than the MOE 20-mer in several extra-hepatic tissues such as kidney, heart, diaphragm, lung, fat, gastrocnemius and quadriceps. Interestingly, the 14-mer cEt ASO showed the best activity in the animal experiments despite significantly lower T(m) and 5-fold reduced activity in cell culture relative to the 20-mer tcDNA and MOE-modified ASOs. Our experiments establish tcDNA as a useful modification for antisense therapeutics and highlight the role of chemical modifications in influencing ASO pharmacology and pharmacokinetic properties in animals.
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Registered trials
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.