Evidence map›Paper›PMID 24196086›Full record

ArticleGene therapy2014

Toxicology study assessing efficacy and safety of repeated administration of lipid/DNA complexes to mouse lung.

E W F W Alton, A C Boyd, S H Cheng, J C Davies, L A Davies, A Dayan, D R Gill, U Griesenbach, T Higgins, S C Hyde and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 38 citations in OpenAlex.

  1. Trial
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  6. Article
  7. Pulmonary gene delivery-Realities and possibilities.Experimental biology and medicine (Maywood, N.J.) · 2021
    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

16 authors at 2 institutions in 1 country.

E W F W Alton1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Department of Gene Therapy, Imperial College, London, UK.
A C Boyd1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
S H ChengGenzyme, a Sanofi Company, Framingham, MA 01701, USA.
J C Davies1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Department of Gene Therapy, Imperial College, London, UK.
L A Davies1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Gene Medicine Research Group, NDCLS, John Radcliffe Hospital, Oxford University, Oxford, UK.
A DayanToxicology Consult, London, UK.
D R Gill1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Gene Medicine Research Group, NDCLS, John Radcliffe Hospital, Oxford University, Oxford, UK.
U Griesenbach1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Department of Gene Therapy, Imperial College, London, UK.
T Higgins1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Department of Gene Therapy, Imperial College, London, UK.
S C Hyde1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Gene Medicine Research Group, NDCLS, John Radcliffe Hospital, Oxford University, Oxford, UK.
J A Innes1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Scottish Adult Cystic Fibrosis Service, Western General Hospital, Edinburgh, UK.
G McLachlan1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Roslin Institute, University of Edinburgh, Edinburgh, UK.
D Porteous1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
I Pringle1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Gene Medicine Research Group, NDCLS, John Radcliffe Hospital, Oxford University, Oxford, UK.
R K ScheuleGenzyme, a Sanofi Company, Framingham, MA 01701, USA.
S Sumner-Jones1] UK CF Gene Therapy Consortium, London, Oxford and Edinburgh, UK [2] Gene Medicine Research Group, NDCLS, John Radcliffe Hospital, Oxford University, Oxford, UK.
Cell and Gene Therapy Catapult · GBJohn Radcliffe Hospital · GB

Funding

Medical Research Council G0100266
6 · The paper itself

Abstract

For gene therapy to improve lung function in cystic fibrosis (CF) subjects, repeated administration of the gene transfer agent over the lifetime of patients is likely to be necessary. This requirement limits the utility of adenoviral and adeno-associated viral vectors (both previously evaluated in CF gene therapy trials) because of induced adaptive immune responses that render repeated dosing ineffective. For CF gene therapy trials, non-viral vectors are currently the only viable option. We previously showed that the cationic lipid formulation GL67A is the most efficient of several non-viral vectors analysed for airway gene transfer. Here, we assessed the efficacy and safety of administering 12 inhaled doses of GL67A complexed with pGM169, a CpG-free plasmid encoding human CFTR complementary DNA, into mice. We show that repeated administration of pGM169/GL67A to murine lungs is feasible, safe and achieves reproducible, dose-related and persistent gene expression (>140 days after each dose) using an aerosol generated by a clinically relevant nebuliser. This study supports progression into the first non-viral multidose lung trial in CF patients.

Indexed as

Genetic TherapyGenetic VectorsPlasmidsAdministration, InhalationAnimalsCombined Modality TherapyCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDisease Models, AnimalDose-Response Relationship, DrugFemaleHumansLipidsLungMaleMiceCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorLipids

Identifiers

PMID24196086
OpenAlexW2166365056

What OpenQuestion holds

Textmetadata
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.