Evidence map›Paper›PMID 31026390›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2019

Restoration of F508-del Function by Transcomplementation: The Partners Meet in the Endoplasmic Reticulum.

Emily Anne Smith Bergbower, Inna Sabirzhanova, Clément Boinot, William B Guggino, Liudmila Cebotaru

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

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.3field-weighted citation impact, top 34% 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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

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

5 authors at 1 institution in 1 country.

Emily Anne Smith BergbowerDepartments of Medicine and Physiology, Johns Hopkins University, Baltimore, USA.
Inna SabirzhanovaDepartments of Medicine and Physiology, Johns Hopkins University, Baltimore, USA.
Clément BoinotDepartments of Medicine and Physiology, Johns Hopkins University, Baltimore, USA.
William B GugginoDepartments of Medicine and Physiology, Johns Hopkins University, Baltimore, USA.
Liudmila CebotaruDepartments of Medicine and Physiology, Johns Hopkins University, Baltimore, USA, lcebotaru@jhmi.edu.
Johns Hopkins University · US

Funding

CF Gene Therapy with adeno-associated viral vectorsR01HL122267 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CEBOTARU, LIUDMILA, GUGGINO, WILLIAM B. · 2016 to 2020
$3.4M
Design of Non-viral Gene Carriers that Overcome Extra- and Intracellular BarriersF32HL103137 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KIM, ANTHONY J. · 2011 to 2012
$102k
Cystic Fibrosis Foundation GUGGIN14XX0NHLBI NIH HHS F32 HL103137NHLBI NIH HHS R01 HL122267NIH HHS R01 HL122267
6 · The paper itself

Abstract

BACKGROUND/

aimsBecause of the small size of adeno-associated virus, AAV, the cystic fibrosis conductance regulator, CFTR, cDNA is too large to fit within AAV and must be truncated. We report here on two truncated versions of CFTR, which, when inserted into AAV1 and used to infect airway cells, rescue F508-del CFTR via transcomplementation. The purpose of this study is to shed light on where in the cell transcomplementation occurs and how it results in close association between the endogenous F508-del and truncated CFTR.

methodsWe treated CF airway cells (CFBE41o

resultsWe show that both F508del and the truncation mutants colocalize in the ER and that both the rescued F508-del and the transcomplementing mutants reach the plasma membrane together. There was significant fluorescence resonance energy transfer (FRET) between F508-del and the transcomplementing mutants within the endoplasmic reticulum (ER), suggesting that transcomplementation occurs through a bimolecular interaction. We found that transcomplementation could increase the Isc in CFBE41o

conclusionWe conclude that the functional rescue of F508-del by transcomplementation occurs via a bimolecular interaction that most likely begins in the ER and continues at the plasma membrane. These results come at an opportune time for developing a gene therapy for CF and offer new treatment options for a wide range of CF patients.

Indexed as

Cell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDependovirusEndoplasmic ReticulumGenetic TherapyHumansRespiratory MucosaSequence DeletionTransfectionCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorBimolecular interactionCystic fibrosisGene therapyTranscomplementationTruncated CFTR

Identifiers

PMID31026390
PMCPMC7097968
OpenAlexW2962756090

What OpenQuestion holds

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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.