ArticleNucleic acids research2015
Splice-shifting oligonucleotide (SSO) mediated blocking of an exonic splicing enhancer (ESE) created by the prevalent c.903+469T>C MTRR mutation corrects splicing and restores enzyme activity in patient cells.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- From N-of-1 to versatility in propionic acidemia: Antisense oligonucleotide-mediated skipping of a constitutiveMolecular therapy. Nucleic acids · 2026Article
- Splice-modulating antisense oligonucleotides targeting a pathogenic intronic variant in adult polyglucosan body disease correct mis-splicing and restore enzyme activity in patient cells.Nucleic acids research · 2025Article
- The U1-70K and SRSF1 interaction is modulated by phosphorylation during the early stages of spliceosome assembly.Protein science : a publication of the Protein Society · 2024Article
- RegulatingMolecular therapy. Nucleic acids · 2024Article
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.Orphanet journal of rare diseases · 2023Article
- Antisense Oligonucleotide Rescue of Deep-Intronic Variants Activating Pseudoexons in the 6-Pyruvoyl-Tetrahydropterin Synthase Gene.Nucleic acid therapeutics · 2022Article
- hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.Frontiers in pharmacology · 2022Review
- Candidate genes and sequence variants for susceptibility to mycobacterial infection identified by whole-exome sequencing.Frontiers in genetics · 2022Article
- Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of erythropoietic protoporphyria.Nucleic acids research · 2020Article
- Aberrant alternative splicing in breast cancer.Journal of molecular cell biology · 2019Review
- Function, clinical application, and strategies of Pre-mRNA splicing in cancer.Cell death and differentiation · 2019Review
- A novel antisense oligonucleotide anchored on the intronic splicing enhancer of hTERT pre-mRNA inhibits telomerase activity and induces apoptosis in glioma cells.Journal of neuro-oncology · 2019Article
- A recurrent COL6A1 pseudoexon insertion causes muscular dystrophy and is effectively targeted by splice-correction therapies.JCI insight · 2019Article
- Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells.Nucleic acids research · 2018Article
- Global identification of hnRNP A1 binding sites for SSO-based splicing modulation.BMC biology · 2016Article
- Article
- Oligonucleotide Therapies: The Past and the Present.Human gene therapy · 2015Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
The prevalent c.903+469T>C mutation in MTRR causes the cblE type of homocystinuria by strengthening an SRSF1 binding site in an ESE leading to activation of a pseudoexon. We hypothesized that other splicing regulatory elements (SREs) are also critical for MTRR pseudoexon inclusion. We demonstrate that the MTRR pseudoexon is on the verge of being recognized and is therefore vulnerable to several point mutations that disrupt a fine-tuned balance between the different SREs. Normally, pseudoexon inclusion is suppressed by a hnRNP A1 binding exonic splicing silencer (ESS). When the c.903+469T>C mutation is present two ESEs abrogate the activity of the ESS and promote pseudoexon inclusion. Blocking the 3'splice site or the ESEs by SSOs is effective in restoring normal splicing of minigenes and endogenous MTRR transcripts in patient cells. By employing an SSO complementary to both ESEs, we were able to rescue MTRR enzymatic activity in patient cells to approximately 50% of that in controls. We show that several point mutations, individually, can activate a pseudoexon, illustrating that this mechanism can occur more frequently than previously expected. Moreover, we demonstrate that SSO blocking of critical ESEs is a promising strategy to treat the increasing number of activated pseudoexons.
Indexed as
Identifiers
What OpenQuestion holds
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.