Evidence map›Paper›PMID 29360847›Full record

ArticlePloS one2018

Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells.

Erika N Sutanto, Amelia Scaffidi, Luke W Garratt, Kevin Looi, Clara J Foo, Michela A Tessari, Richard A Janssen, David F Fischer, Stephen M Stick, Anthony Kicic and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2018. 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
0.4field-weighted citation impact, top 37% of its field
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, 4 citations in OpenAlex.

  1. Basic Science Perspective on Engineering and Modeling the Large Airways.Advances in experimental medicine and biology · 2023
    Article
  2. Article
  3. Review
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

11 authors at 5 institutions in 2 countries.

Erika N SutantoTelethon Kids Institute, the University of Western Australia, Nedlands, Western Australia, Australia.
Amelia ScaffidiOffice of Research Enterprise, The University of Western Australia, Nedlands, Western Australia, Australia.
Luke W GarrattTelethon Kids Institute, the University of Western Australia, Nedlands, Western Australia, Australia.
Kevin LooiTelethon Kids Institute, the University of Western Australia, Nedlands, Western Australia, Australia.
Clara J FooSchool of Paediatrics and Child Health, The University of Western Australia, Nedlands, Western Australia, Australia.
Michela A TessariGalapagos BV, 2300 AC, Leiden, the Netherlands.
Richard A JanssenGalapagos BV, 2300 AC, Leiden, the Netherlands.
David F FischerCharles River Laboratories, Leiden, the Netherlands.
Stephen M StickTelethon Kids Institute, the University of Western Australia, Nedlands, Western Australia, Australia.
Anthony KicicTelethon Kids Institute, the University of Western Australia, Nedlands, Western Australia, Australia.ORCID 0000-0002-0008-9733
AREST CF
The Kids Research Institute Australia · AUGalapagos (Netherlands) · NLThe University of Western Australia · AUCharles River Laboratories (Netherlands) · NLRoyal Children's Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMutations in the cystic fibrosis transmembrane regulator (CFTR) gene can reduce function of the CFTR ion channel activity and impair cellular chloride secretion. The gold standard method to assess CFTR function of ion transport using the Ussing chamber requires a high number of airway epithelial cells grown at air-liquid interface, limiting the application of this method for high throughput screening of potential therapeutic compounds in primary airway epithelial cells (pAECs) featuring less common CFTR mutations. This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC.

methodsPediatric pAECs derived from children with CF (pAECCF) were established and expanded as monolayer cultures, before seeding into 96-well plates for the halide assay. Cells were then transduced with an adenoviral construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in combination with either wild-type CFTR (WT-CFTR) or p.Phe508del CFTR. Four days post transduction, cells were stimulated with forskolin and genistein, and assessed for quenching of the eYFP signal following injection of iodide solution into the assay media.

resultsData showed that pAECCF can express eYFP at high efficiency following transduction with the eYFP construct. The halide assay was able to discriminate functional restoration of CFTR in pAECCF treated with either WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor-associated protein 31 shRNAs. SIGNIFICANCE: The current study demonstrates that the halide assay can be adapted for pediatric pAECCF to evaluate restoration of CFTR function. With the ongoing development of small molecules to modulate the folding and/or activity of various mutated CFTR proteins, this halide assay presents a small-scale personalized screening platform that could assess therapeutic potential of molecules across a broad range of CFTR mutations.

Indexed as

AdenoviridaeBronchiCells, CulturedChildCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGenetic VectorsHumansPhenylalanineProtein TransportTracheaTransduction, GeneticCystic Fibrosis Transmembrane Conductance RegulatorPhenylalanine

Identifiers

PMID29360847
PMCPMC5779693
OpenAlexW2786747777

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.