Evidence map›Paper›PMID 41015699›Full record

ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2026

Identity, functional consequences, and context effects of amino acids inserted during suppression of CFTR nonsense mutations.

Kari Thrasher, Jianguo Chen, Lianwu Fu, Dominique Benson, Jenna Ekstrom, Audra A Hargett, Matthew B Renfrow, Steven M Rowe, Kim M Keeling, David M Bedwell

Abstract read
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In one paragraph

Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. RNAViruses · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Kari ThrasherDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Jianguo ChenDepartments of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Departments of Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Lianwu FuDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Departments of Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Dominique BensonDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Jenna EkstromDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Audra A HargettDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Matthew B RenfrowDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Steven M RoweDepartments of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Departments of Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Kim M KeelingDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Departments of Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
David M BedwellDepartments of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Departments of Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: dbedwell@uab.edu.

Funding

UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AMIT GAGGAR · 2007 to 2026
$23.0M
NIDDK NIH HHS P30 DK072482
6 · The paper itself

Abstract

backgroundCystic fibrosis patients who carry a CFTR nonsense allele often express negligible CFTR protein, and thus, are unresponsive to CFTR modulators. Nonsense suppression (also called readthrough) is an emerging therapeutic approach for this patient subgroup that uses small molecules to suppress translation termination at in-frame premature termination codons (PTCs) and rescue full-length, functional CFTR protein. This study examines mechanistic aspects of readthrough at six CFTR PTCs commonly found in CF patients.

methodsCFTR expression and chloride conductance were used to assess the responsiveness of six different CFTR PTCs to G418-mediated readthrough. LC-MS/MS was used to identify the CFTR variant proteins generated by readthrough of PTCs in their native, local CFTR mRNA sequence context. For each CFTR variant protein identified, the abundance, processing, activity, and responsiveness to CFTR modulators were characterized.

resultsCFTR expression and function varied widely among PTCs, with UGA generally being the most responsive to G418-mediated readthrough. The amino acids incorporated at PTCs during G418-induced readthrough also varied, depending on the PTC and its surrounding local mRNA context. Modulators stabilized and enhanced the abundance and activity of most CFTR variant proteins generated by PTC readthrough, with many variant proteins reaching WT CFTR activity.

conclusionsNonsense suppression therapy shows promise as a treatment for CF patients who carry a PTC, especially when combined with current CFTR modulators. Mechanistic insights of readthrough gleaned from this study can be used to develop better therapeutic strategies for treating CF patients who carry a nonsense mutation.

Indexed as

Amino AcidsCodon, NonsenseCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansAmino AcidsCFTR protein, humanCodon, NonsenseCystic Fibrosis Transmembrane Conductance RegulatorCFTRNonsense suppressionReadthrough

Identifiers

PMID41015699
PMCPMC12614629

What OpenQuestion holds

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Registered trials

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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.