ArticleNucleic acids research2022
Palmitic acid conjugation enhances potency of tricyclo-DNA splice switching oligonucleotides.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05753462 (Phase 1/2a, Monocentric, Open Label Study to Evaluate the Safety, PK and PD of SQY51 in Paediatric and Adult Patients With a Genetically Confirmed Diagnosis of Duchenne Muscular Dystrophy), which is not on this map. Cited by 30 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1/2a, Monocentric, Open Label Study to Evaluate the Safety, PK and PD of SQY51 in Paediatric and Adult Patients With a Genetically Confirmed Diagnosis of Duchenne Muscular Dystrophy
Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application toMolecular therapy. Nucleic acids · 2026Article
- Givinostat enhances antisense oligonucleotide efficacy in theMolecular therapy. Nucleic acids · 2026Article
- Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.Molecular diagnosis & therapy · 2026Review
- 5'-Palmitate Lipid and Internal LNA-Piperidyl Triesters Enhance the RNA Affinity and Activity of Splice-Switching Oligonucleotides.Journal of the American Chemical Society · 2026Article
- Identification and functional validation of intracellular protein partners of phosphorothioate splice-switching oligonucleotides using AP-MS.Molecular therapy. Nucleic acids · 2026Article
- Improving angiogenesis ameliorates the efficacy of ASO-based exon skipping for the treatment of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2026Article
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Antisense RNA therapies for muscular dystrophies.Journal of neuromuscular diseases · 2026Review
- Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs.Advanced healthcare materials · 2026Review
- Systemic distribution of tricyclo-DNA antisense oligonucleotide following intratracheal instillation in the mouse.NAR molecular medicine · 2026Article
- Behavioral improvement in dystrophicMolecular therapy. Nucleic acids · 2025Article
- Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Valproic Acid Improves Antisense-Mediated Exon-Skipping Efficacy inInternational journal of molecular sciences · 2025Article
- Use of Tricyclo-DNA Antisense Oligonucleotides for Exon-Skipping.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model.Nature communications · 2024Article
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Networking to OptimizeBiomedicines · 2023Article
- Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues.International journal of molecular sciences · 2023Article
- Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotides alleviates emotional deficits inMolecular therapy. Nucleic acids · 2023Article
- Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models.Cells · 2023Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tricyclo-DNA (tcDNA) is a conformationally constrained oligonucleotide analog that has demonstrated great therapeutic potential as antisense oligonucleotide (ASO) for several diseases. Like most ASOs in clinical development, tcDNA were modified with phosphorothioate (PS) backbone for therapeutic purposes in order to improve their biodistribution by enhancing association with plasma and cell protein. Despite the advantageous protein binding properties, systemic delivery of PS-ASO remains limited and PS modifications can result in dose limiting toxicities in the clinic. Improving extra-hepatic delivery of ASO is highly desirable for the treatment of a variety of diseases including neuromuscular disorders such as Duchenne muscular dystrophy. We hypothesized that conjugation of palmitic acid to tcDNA could facilitate the delivery of the ASO from the bloodstream to the interstitium of the muscle tissues. We demonstrate here that palmitic acid conjugation enhances the potency of tcDNA-ASO in skeletal and cardiac muscles, leading to functional improvement in dystrophic mice with significantly reduced dose of administered ASO. Interestingly, palmitic acid-conjugated tcDNA with a full phosphodiester backbone proved effective with a particularly encouraging safety profile, offering new perspectives for the clinical development of PS-free tcDNA-ASO for neuromuscular diseases.
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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.