ArticlePLoS genetics2016
Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Molecular mechanisms and therapeutic strategies for the recurrent F9 (c.520 + 13 A > G) variant in hemophilia B.Human genomics · 2026Article
- A deep intronic mutation causes RAD50 deficiency through an unusual mechanism of distant exon activation.The Journal of clinical investigation · 2024Article
- All exons are not created equal-exon vulnerability determines the effect of exonic mutations on splicing.Nucleic acids research · 2024Article
- Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.PloS one · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Dissection of pleiotropic effects of variants in and adjacent to F8 exon 19 and rescue of mRNA splicing and protein function.American journal of human genetics · 2021Article
- Profiling of cis- and trans-acting factors supporting noncanonical splice site activation.RNA biology · 2021Article
- Alternative RNA Splicing in Fatty Liver Disease.Frontiers in endocrinology · 2021Review
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- Therapeutic approaches to treat human spliceosomal diseases.Current opinion in biotechnology · 2019Review
- Splicing Mutations Impairing CDKL5 Expression and Activity Can be Efficiently Rescued by U1snRNA-Based Therapy.International journal of molecular sciences · 2019Article
- Rescue of spinal muscular atrophy mouse models with AAV9-Exon-specific U1 snRNA.Nucleic acids research · 2019Article
- Splicing dysregulation contributes to the pathogenicity of several F9 exonic point variants.Molecular genetics & genomic medicine · 2019Article
- Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies.International journal of molecular sciences · 2019Review
- An Altered Splicing Registry Explains the Differential ExSpeU1-Mediated Rescue of Splicing Mutations Causing Haemophilia A.Frontiers in genetics · 2019Article
- Program and Book of the 15th Interuniversity Institute of Myology Meeting - Assisi (Italy), 2018.European journal of translational myology · 2018Article
- Exon-specific U1 snRNAs improve ELP1 exon 20 definition and rescue ELP1 protein expression in a familial dysautonomia mouse model.Human molecular genetics · 2018Article
- The somatic FAH C.1061C>A change counteracts the frequent FAH c.1062+5G>A mutation and permits U1snRNA-based splicing correction.Journal of human genetics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function. Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level. We have identified a series of disease-causing splicing mutations in coagulation factor IX (FIX) exon 5 that are completely recovered by a modified U1snRNP particle, through an SRSF2-dependent enhancement mechanism. We discovered that synonymous mutations and missense substitutions associated to a partial FIX secretion defect represent targets for this therapy as the resulting spliced-corrected proteins maintains normal FIX coagulant specific activity. Thus, splicing and protein alterations contribute to define at the molecular level the disease-causing effect of a number of exonic mutations in coagulation FIX exon 5. In addition, our results have a significant impact in the development of splicing-switching therapies in particular for mutations that affect both splicing and protein function where increasing the amount of a correctly spliced protein can circumvent the basic functional defects.
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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.