ArticleThe Journal of clinical investigation2022
Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Liquid biopsy and health-related quality of life in cancers: a systematic review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Pooled it
- Applications of circulating tumor DNA in unresectable and advanced non-small cell lung cancer immunotherapy: from stratification to therapeutic guidance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- KRAS and TP53 Circulating Tumor DNA are Prognostic in Localized Pancreatic Cancer.Annals of surgical oncology · 2026Article
- Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.Pharmaceutics · 2026Review
- Identification of small molecules that enhance aminoglycoside-mediated suppression ofMolecular therapy. Oncology · 2026Article
- Harnessing biomarkers to guide immunotherapy in esophageal cancer: toward precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations.Cellular and molecular life sciences : CMLS · 2026Article
- Novel eRF3a degrader enhances gentamicin-induced premature termination codon readthrough in epidermolysis bullosa.Molecular therapy. Nucleic acids · 2025Article
- Review
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.RNA (New York, N.Y.) · 2025Review
- Anticodon-edited tRNA enables translational readthrough of COL4A5 premature termination codons.PloS one · 2025Article
- Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules.Nature genetics · 2024Article
- Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations.Nature communications · 2024Article
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Misincorporations of amino acids in p53 in human cells at artificially constructed termination codons in the presence of the aminoglycoside Gentamicin.Frontiers in genetics · 2024Article
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- Air-Liquid interface cultures to model drug delivery through the mucociliary epithelial barrier.Advanced drug delivery reviews · 2023Review
- Theratyping of the Rare CFTR Genotype A559T in Rectal Organoids and Nasal Cells Reveals a Relevant Response to Elexacaftor (VX-445) and Tezacaftor (VX-661) Combination.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
The vast majority of people with cystic fibrosis (CF) are now eligible for CF transmembrane regulator (CFTR) modulator therapy. The remaining individuals with CF harbor premature termination codons (PTCs) or rare CFTR variants with limited treatment options. Although the clinical modulator response can be reliably predicted using primary airway epithelial cells, primary cells carrying rare CFTR variants are scarce. To overcome this obstacle, cell lines can be created by overexpression of mouse Bmi-1 and human TERT (hTERT). Using this approach, we developed 2 non-CF and 6 CF airway epithelial cell lines, 3 of which were homozygous for the W1282X PTC variant. The Bmi-1/hTERT cell lines recapitulated primary cell morphology and ion transport function. The 2 F508del-CFTR cell lines responded robustly to CFTR modulators, which was mirrored in the parent primary cells and in the cell donors' clinical response. Cereblon E3 ligase modulators targeting eukaryotic release factor 3a (eRF3a) rescued W1282X-CFTR function to approximately 20% of WT levels and, when paired with G418, rescued G542X-CFTR function to approximately 50% of WT levels. Intriguingly, eRF3a degraders also diminished epithelial sodium channel (ENaC) function. These studies demonstrate that Bmi-1/hTERT cell lines faithfully mirrored primary cell responses to CFTR modulators and illustrate a therapeutic approach to rescue CFTR nonsense mutations.
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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.