ArticleGenome biology2018
Antisense suppression of the nonsense mediated decay factor Upf3b as a potential treatment for diseases caused by nonsense mutations.
Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 52 citations in OpenAlex.
- Beyond quality control: biological roles of nonsense-mediated RNA decay.The EMBO journal · 2026Review
- Nonsense-mediated mRNA decay: friend or foe in cancer biology?Cell communication and signaling : CCS · 2026Review
- Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer.Cell communication and signaling : CCS · 2025Review
- Cell type- and factor-specific nonsense-mediated RNA decay.Nucleic acids research · 2025Article
- Overgrowth-intellectual disability disorders: progress in biology, patient advocacy and innovative therapies.Disease models & mechanisms · 2025Review
- Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.RNA (New York, N.Y.) · 2025Review
- Therapeutic Nonsense Suppression Modalities: From Small Molecules to Nucleic Acid-Based Approaches.Biomedicines · 2024Review
- Human disease-causing mutations result in loss of leiomodin 2 through nonsense-mediated mRNA decay.PLoS genetics · 2024Article
- A Novel Four-Gene Signature Based on Nonsense-Mediated RNA Decay for Predicting Prognosis in Hepatocellular Carcinoma: Bioinformatics Analysis and Functional Validation.Journal of hepatocellular carcinoma · 2024Article
- En route towards a personalized medicine approach: Innovative therapeutic modalities for connective tissue disorders.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells.Life science alliance · 2023Article
- Drug Discovery Perspectives of Antisense Oligonucleotides.Biomolecules & therapeutics · 2023Review
- Recoding of Nonsense Mutation as a Pharmacological Strategy.Biomedicines · 2023Review
- Antisense Oligonucleotide Therapeutics for Cystic Fibrosis: Recent Developments and Perspectives.Molecules and cells · 2023Review
- Targeting nonsense-mediated RNA decay does not increase progranulin levels in the Grn R493X mouse model of frontotemporal dementia.PloS one · 2023Article
- SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis.Nucleic acids research · 2022Article
- Nonviral delivery systems for antisense oligonucleotide therapeutics.Biomaterials research · 2022Review
- Diverse Roles of the Exon Junction Complex Factors in the Cell Cycle, Cancer, and Neurodevelopmental Disorders-Potential for Therapeutic Targeting.International journal of molecular sciences · 2022Review
- Gene-specific nonsense-mediated mRNA decay targeting for cystic fibrosis therapy.Nature communications · 2022Article
- Human UPF3A and UPF3B enable fault-tolerant activation of nonsense-mediated mRNA decay.The EMBO journal · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAbout 11% of all human genetic diseases are caused by nonsense mutations that generate premature translation termination codons (PTCs) in messenger RNAs (mRNA). PTCs not only lead to the production of truncated proteins, but also often result in decreased mRNA abundance due to nonsense-mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an attractive therapeutic approach for the treatment of diseases caused by nonsense mutations, NMD also regulates the expression of 10-20% of the normal transcriptome.
resultsHere, we investigate whether NMD can be inhibited to stabilize mutant mRNAs, which may subsequently produce functional proteins, without having a major impact on the normal transcriptome. We develop antisense oligonucleotides (ASOs) to systematically deplete each component in the NMD pathway. We find that ASO-mediated depletion of each NMD factor elicits different magnitudes of NMD inhibition in vitro and are differentially tolerated in normal mice. Among all of the NMD factors, Upf3b depletion is well tolerated, consistent with previous reports that UPF3B is not essential for development and regulates only a subset of the endogenous NMD substrates. While minimally impacting the normal transcriptome, Upf3b-ASO treatment significantly stabilizes the PTC-containing dystrophin mRNA in mdx mice and coagulation factor IX mRNA in a hemophilia mouse model. Furthermore, when combined with reagents promoting translational read-through, Upf3b-ASO treatment leads to the production of functional factor IX protein in hemophilia mice.
conclusionsThese data demonstrate that ASO-mediated reduction of the NMD factor Upf3b could be an effective and safe approach for the treatment of diseases caused by nonsense mutations.
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.