ArticleNucleic acids research2019
Rescue of spinal muscular atrophy mouse models with AAV9-Exon-specific U1 snRNA.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models.Gene therapy · 2022Pooled it
- Correction of aberrant splicing caused by intronic CAPN3 pathogenic variants using RNA-targeted therapeutic strategies in limb-girdle muscular dystrophy type R1.Orphanet journal of rare diseases · 2026Article
- Molecular mechanisms and therapeutic strategies for the recurrent F9 (c.520 + 13 A > G) variant in hemophilia B.Human genomics · 2026Article
- Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy.Nature communications · 2025Article
- Utargetome: A targetome prediction tool for modified U1-snRNAs to identify distal-target positions with improved selectivity.PLoS computational biology · 2025Article
- Rescue of a panel of Hemophilia A-causing 5'ss splicing mutations by unique Exon-specific U1snRNA variants.Molecular medicine (Cambridge, Mass.) · 2025Article
- Treating neuromuscular diseases: unveiling gene therapy breakthroughs and pioneering future applications.Journal of biomedical science · 2025Review
- Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.Molecular medicine (Cambridge, Mass.) · 2025Article
- Gene hydrogel platforms for targeted skin therapy: bridging hereditary disorders, chronic wounds, and immune related skin diseases.Frontiers in drug delivery · 2025Review
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.Nucleic acids research · 2024Article
- Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy.Nature biomedical engineering · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.Nature reviews. Genetics · 2023Review
- DG9-conjugated morpholino rescues phenotype in SMA mice by reaching the CNS via a subcutaneous administration.JCI insight · 2023Article
- Counteracting the Common Shwachman-Diamond Syndrome-CausingInternational journal of molecular sciences · 2023Article
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Adeno-Associated Viral Vectors as Versatile Tools for Neurological Disorders: Focus on Delivery Routes and Therapeutic Perspectives.Biomedicines · 2022Review
- Optogenetics for Understanding and Treating Brain Injury: Advances in the Field and Future Prospects.International journal of molecular sciences · 2022Review
- OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spfMolecular medicine (Cambridge, Mass.) · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal Muscular Atrophy results from loss-of-function mutations in SMN1 but correcting aberrant splicing of SMN2 offers hope of a cure. However, current splice therapy requires repeated infusions and is expensive. We previously rescued SMA mice by promoting the inclusion of a defective exon in SMN2 with germline expression of Exon-Specific U1 snRNAs (ExspeU1). Here we tested viral delivery of SMN2 ExspeU1s encoded by adeno-associated virus AAV9. Strikingly the virus increased SMN2 exon 7 inclusion and SMN protein levels and rescued the phenotype of mild and severe SMA mice. In the severe mouse, the treatment improved the neuromuscular function and increased the life span from 10 to 219 days. ExspeU1 expression persisted for 1 month and was effective at around one five-hundredth of the concentration of the endogenous U1snRNA. RNA-seq analysis revealed our potential drug rescues aberrant SMA expression and splicing profiles, which are mostly related to DNA damage, cell-cycle control and acute phase response. Vastly overexpressing ExspeU1 more than 100-fold above the therapeutic level in human cells did not significantly alter global gene expression or splicing. These results indicate that AAV-mediated delivery of a modified U1snRNP particle may be a novel therapeutic option against SMA.
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