ArticleNucleic acids research2002
Antisense properties of tricyclo-DNA.
Article in Nucleic acids research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 88 citations in OpenAlex.
- Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application toMolecular therapy. Nucleic acids · 2026Article
- Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology.Molecules (Basel, Switzerland) · 2026Review
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- An Overview of Recent Advances and Clinical Applications of Exon Skipping and Splice Modulation for Muscular Dystrophy and Various Genetic Diseases.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction.International journal of molecular sciences · 2024Article
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Towards combining backbone and sugar constraint in 3'-3' bis-phosphonate tethered 2'-4' bridged LNA oligonucleotide trimers.RSC advances · 2024Article
- A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position.International journal of molecular sciences · 2024Article
- Evaluation of Chemically Modified Nucleic Acid Analogues for Splice Switching Application.ACS omega · 2023Review
- Review
- The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Palmitic acid conjugation enhances potency of tricyclo-DNA splice switching oligonucleotides.Nucleic acids research · 2022Article
- Chemistry of Peptide-Oligonucleotide Conjugates: A Review.Molecules (Basel, Switzerland) · 2021Review
- The powerful world of antisense oligonucleotides: From bench to bedside.Wiley interdisciplinary reviews. RNA · 2020Review
- Synthesis and Evaluation of Artificial Nucleic Acid Bearing an Oxanorbornane Scaffold.Molecules (Basel, Switzerland) · 2020Article
- Identifying and Avoiding tcDNA-ASO Sequence-Specific Toxicity for the Development of DMD Exon 51 Skipping Therapy.Molecular therapy. Nucleic acids · 2020Article
- NMR solution structure of tricyclo-DNA containing duplexes: insight into enhanced thermal stability and nuclease resistance.Nucleic acids research · 2019Article
- Antisense oligonucleotides for the treatment of cardiomyopathy in Duchenne muscular dystrophy.American journal of translational research · 2019Review
- Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers.Molecular therapy. Nucleic acids · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tricyclo (tc)-DNA belongs to the class of conformationally constrained DNA analogs that show enhanced binding properties to DNA and RNA. We prepared tc-oligonucleotides up to 17 nt in length, and evaluated their binding efficiency and selectivity towards complementary RNA, their biological stability in serum, their RNase H inducing potential and their antisense activity in a cellular assay. Relative to RNA or 2'-O-Me-phosphorothioate (PS)-RNA, fully modified tc-oligodeoxynucleotides, 10-17 nt in length, show enhanced selectivity and enhanced thermal stability by approximately 1 degrees C/modification in binding to RNA targets. Tricyclodeoxyoligonucleotides are completely stable in heat-deactivated fetal calf serum at 37 degree C. Moreover, tc-DNA-RNA duplexes are not substrates for RNase H. To test for antisense effects in vivo, we used HeLa cell lines stably expressing the human beta-globin gene with two different point mutations in the second intron. These mutations lead to the inclusion of an aberrant exon in beta-globin mRNA. Lipofectamine-mediated delivery of a 17mer tc-oligodeoxynucleotide complementary to the 3'-cryptic splice site results in correction of aberrant splicing already at nanomolar concentrations with up to 100-fold enhanced efficiency relative to a 2'-O-Me-PS-RNA oligonucleotide of the same length and sequence. In contrast to 2'-O-Me-PS-RNA, tc-DNA shows antisense activity even in the absence of lipofectamine, albeit only at much higher oligonucleotide concentrations.
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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.