ArticleMolecular therapy. Nucleic acids2017
Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Enhanced splicing modulation by NMA-modified antisense oligonucleotides.Nucleic acids research · 2026Article
- Use of Tricyclo-DNA Antisense Oligonucleotides for Exon-Skipping.Methods in molecular biology (Clifton, N.J.) · 2025Article
- 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
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Morpholino-Mediated Exon Inclusion for Spinal Muscular Atrophy (SMA).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Therapeutic strategy for spinal muscular atrophy by combining gene supplementation and genome editing.Nature communications · 2024Article
- Antisense oligonucleotides and their applications in rare neurological diseases.Frontiers in neuroscience · 2024Review
- Evaluation of Chemically Modified Nucleic Acid Analogues for Splice Switching Application.ACS omega · 2023Review
- Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotides alleviates emotional deficits inMolecular therapy. Nucleic acids · 2023Article
- DG9-conjugated morpholino rescues phenotype in SMA mice by reaching the CNS via a subcutaneous administration.JCI insight · 2023Article
- Partial Restoration of Brain Dystrophin and Behavioral Deficits by Exon Skipping in the Muscular Dystrophy X-Linked (mdx) Mouse.Annals of neurology · 2022Article
- Palmitic acid conjugation enhances potency of tricyclo-DNA splice switching oligonucleotides.Nucleic acids research · 2022Article
- Common and Rare 5'UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics.Frontiers in cardiovascular medicine · 2022Review
- Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation.Cancers · 2021Review
- High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.International journal of molecular sciences · 2021Article
- Review
- RNA in spinal muscular atrophy: therapeutic implications of targeting.Expert opinion on therapeutic targets · 2020Review
- Comparison of the efficacy of MOE and PMO modifications of systemic antisense oligonucleotides in a severe SMA mouse model.Nucleic acids research · 2020Article
- Identifying and Avoiding tcDNA-ASO Sequence-Specific Toxicity for the Development of DMD Exon 51 Skipping Therapy.Molecular therapy. Nucleic acids · 2020Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is a recessive disease caused by mutations in the SMN1 gene, which encodes the protein survival motor neuron (SMN), whose absence dramatically affects the survival of motor neurons. In humans, the severity of the disease is lessened by the presence of a gene copy, SMN2. SMN2 differs from SMN1 by a C-to-T transition in exon 7, which modifies pre-mRNA splicing and prevents successful SMN synthesis. Splice-switching approaches using antisense oligonucleotides (AONs) have already been shown to correct this SMN2 gene transition, providing a therapeutic avenue for SMA. However, AON administration to the CNS presents additional hurdles. In this study, we show that systemic delivery of tricyclo-DNA (tcDNA) AONs in a type III SMA mouse augments retention of exon 7 in SMN2 mRNA both in peripheral organs and the CNS. Mild type III SMA mice were selected as opposed to the severe type I model in order to test tcDNA efficacy and their ability to enter the CNS after maturation of the blood brain barrier (BBB). Furthermore, subcutaneous treatment significantly improved the necrosis phenotype and respiratory function. In summary, our data support that tcDNA oligomers effectively cross the blood-brain barrier and offer a promising systemic alternative for treating SMA.
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