ArticleHuman molecular genetics2012
An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing defects.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 101 citations in OpenAlex.
- Minigene-based characterization and classification of splice-associated variants in succinate dehydrogenase B.NPJ precision oncology · 2026Article
- 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
- Using RNA-targeting CRISPR-Cas13 and engineered U1 systems to targetMolecular therapy. Nucleic acids · 2026Article
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Extracellular Vesicle-Mediated U1 snRNA Delivery Restores Aberrant Pre-mRNA Splicing in Human Cells.Biomolecules · 2026Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- 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
- RNA splicing in bone diseases: mechanisms, pathogenesis and therapeutics.Acta biochimica Polonica · 2025Review
- Splicing analysis of STAT3 tandem donor suggests non-canonical binding registers for U1 and U6 snRNAs.Nucleic acids research · 2024Article
- Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells.International journal of nanomedicine · 2024Review
- Characterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohort.Human mutation · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders.Cardiovascular research · 2023Review
- Engineered U1 snRNAs to modulate alternatively spliced exons.Methods (San Diego, Calif.) · 2022Article
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Exon-independent recruitment of SRSF1 is mediated by U1 snRNP stem-loop 3.The EMBO journal · 2022Article
- Autosomal dominant optic atrophy: A novel treatment forMolecular therapy. Nucleic acids · 2021Article
- Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation.RNA (New York, N.Y.) · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A significant proportion of disease-causing mutations affect precursor-mRNA splicing, inducing skipping of the exon from the mature transcript. Using F9 exon 5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1 small nuclear RNA (snRNA). In minigene expression systems, loading of U1 snRNA by complementarity to the normal or mutated donor splice sites (5'ss) corrected the exon skipping caused by mutations at the polypyrimidine tract of the acceptor splice site, at the consensus 5'ss or at exonic regulatory elements. To improve specificity and reduce potential off-target effects, we developed U1 snRNA variants targeting non-conserved intronic sequences downstream of the 5'ss. For each gene system, we identified an exon-specific U1 snRNA (ExSpeU1) able to rescue splicing impaired by the different types of mutations. Through splicing-competent cDNA constructs, we demonstrated that the ExSpeU1-mediated splicing correction of several F9 mutations results in complete restoration of secreted functional factor IX levels. Furthermore, two ExSpeU1s for SMA improved SMN exon 7 splicing in the chromosomal context of normal cells. We propose ExSpeU1s as a novel therapeutic strategy to correct, in several human disorders, different types of splicing mutations associated with defective exon definition.
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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.