ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Preclinical PK and PD studies on 2'-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 137 citations in OpenAlex.
- Antisense RNA therapies for muscular dystrophies.Journal of neuromuscular diseases · 2026Review
- A historical perspective on the development of antisense oligonucleotide treatments for Duchenne muscular dystrophy and spinal muscular atrophy.Journal of neuromuscular diseases · 2026Review
- Advancing adeno-associated virus for Duchenne muscular dystrophy treatment: Moving beyond rodent models.Molecular therapy. Methods & clinical development · 2025Article
- Review
- The endosomal escape vehicle platform enhances delivery of oligonucleotides in preclinical models of neuromuscular disorders.Molecular therapy. Nucleic acids · 2023Article
- A Systemically Administered Unconjugated Antisense Oligonucleotide Targeting DUX4 Improves Muscular Injury and Motor Function in FSHD Model Mice.Biomedicines · 2023Article
- Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach.Scientific reports · 2023Article
- Efficient Downregulation ofNucleic acid therapeutics · 2023Article
- Duchenne muscular dystrophy: disease mechanism and therapeutic strategies.Frontiers in physiology · 2023Review
- A cell-penetrating peptide enhances delivery and efficacy of phosphorodiamidate morpholino oligomers inMolecular therapy. Nucleic acids · 2022Article
- Renadirsen, a Novel 2'OMeRNA/ENACurrent issues in molecular biology · 2021Article
- Therapeutic Modulation of RNA Splicing in Malignant and Non-Malignant Disease.Trends in molecular medicine · 2021Review
- Antisense oligonucleotide technology can be used to investigate a circular but not linear RNA-mediated function for its encoded gene locus.Science China. Life sciences · 2021Article
- Delivery of oligonucleotide-based therapeutics: challenges and opportunities.EMBO molecular medicine · 2021Review
- Designed U7 snRNAs inhibitMolecular therapy. Nucleic acids · 2021Article
- Fine Tuning of Phosphorothioate Inclusion in 2'-O-Methyl Oligonucleotides Contributes to Specific Cell Targeting for Splice-Switching Modulation.Frontiers in physiology · 2021Article
- Optimization of antisense-mediated exon skipping for Duchenne muscular dystrophy.Gene therapy · 2020Review
- Premature termination codons in theProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy.Yonsei medical journal · 2020Review
- Using a State-of-the-Art Toolbox to Evaluate Molecular and Functional Readouts of Antisense Oligonucleotide-Induced Exon Skipping inNucleic acid therapeutics · 2020Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Antisense oligonucleotides (AONs) are being developed as RNA therapeutic molecules for Duchenne muscular dystrophy. For oligonucleotides with the 2'-O-methyl-phosphorothioate (2OMePS) RNA chemistry, proof of concept has been obtained in patient-specific muscle cell cultures, the mouse and dog disease models, and recently by local administration in Duchenne patients. To further explore the pharmacokinetic (PK)/pharmacodynamic (PD) properties of this chemical class of oligonucleotides, we performed a series of preclinical studies in mice. The results demonstrate that the levels of oligonucleotides in dystrophin-deficient muscle fibers are much higher than in healthy fibers, leading to higher exon-skipping levels. Oligonucleotide levels and half-life differed for specific muscle groups, with heart muscle showing the lowest levels but longest half-life (approximately 46 days). Intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) delivery methods were directly compared. For each method, exon-skipping and novel dystrophin expression were observed in all muscles, including arrector pili smooth muscle in skin biopsies. After i.v. administration, the oligonucleotide peak levels in plasma, liver, and kidney were higher than after s.c. or i.p. injections. However, as the bioavailability was similar, and the levels of oligonucleotide, exon-skipping, and dystrophin steadily accumulated overtime after s.c. administration, we selected this patient-convenient delivery method for future clinical study protocols.
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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.