Evidence map›Paper›PMID 30022127›Full record

ArticleGene therapy2018

The murine lung as a factory to produce secreted intrapulmonary and circulatory proteins.

Michael C Paul-Smith, Kamila M Pytel, Jean-François Gelinas, Jenny McIntosh, Ian Pringle, Lee Davies, Mario Chan, Cuixiang Meng, Robyn Bell, Lidia Cammack and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Progress in Respiratory Gene Therapy.Human gene therapy · 2022
    Review
  6. Article
  7. Review
  8. Article
  9. Pulmonary gene delivery-Realities and possibilities.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  10. Article
  11. Article
  12. Article
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

20 authors at 3 institutions in 3 countries.

Michael C Paul-SmithDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Kamila M PytelDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Jean-François GelinasUK Cystic Fibrosis Gene Therapy Consortium, London, UK.ORCID http://orcid.org/0000-0003-3454-5781
Jenny McIntoshDepartment of Haematology, University College London Cancer Institute, London, UK.
Ian PringleUK Cystic Fibrosis Gene Therapy Consortium, London, UK.
Lee DaviesUK Cystic Fibrosis Gene Therapy Consortium, London, UK.
Mario ChanDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Cuixiang MengDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Robyn BellDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Lidia CammackDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Caroline MoranDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Loren CameronDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Makoto InoueID Pharma Co. Ltd. (DNAVEC Centre), Tsukuba, Japan.
Shu TsugumineID Pharma Co. Ltd. (DNAVEC Centre), Tsukuba, Japan.
Takashi HironakaID Pharma Co. Ltd. (DNAVEC Centre), Tsukuba, Japan.
Deborah R GillUK Cystic Fibrosis Gene Therapy Consortium, London, UK.
Stephen C HydeUK Cystic Fibrosis Gene Therapy Consortium, London, UK.
Amit NathwaniDepartment of Haematology, University College London Cancer Institute, London, UK.
Eric W F W AltonDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK. e.alton@imperial.ac.uk.
Uta GriesenbachDepartment of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, UK.
Cystic Fibrosis Trust · GBID Pharma (Japan) · JPLondon Cancer · GB

Funding

DIFFERENTIATION SIGNAL TRANSDUCTION IN MYELOID LEUKEMIAK08CA001352 · NCI · DANA-FARBER CANCER INSTITUTE · PI STONE, RICHARD M · 1990 to 1994
–
Medical Research Council MC_PC_12015Medical Research Council (MRC) G01352
6 · The paper itself

Abstract

We have shown that a lentiviral vector (rSIV.F/HN) pseudotyped with the F and HN proteins from Sendai virus generates high levels of intracellular proteins after lung transduction. Here, we evaluate the use of rSIV.F/HN for production of secreted proteins. We assessed whether rSIV.F/HN transduction of the lung generates therapeutically relevant levels of secreted proteins in the lung and systemic circulation using human α1-anti-trypsin (hAAT) and factor VIII (hFVIII) as exemplars. Sedated mice were transduced with rSIV.F/HN carrying either the secreted reporter gene Gaussia luciferase or the hAAT or hFVIII cDNAs by nasal sniffing. rSIV.F/HN-hAAT transduction lead to therapeutically relevant hAAT levels (70 μg/ml) in epithelial lining fluid, with stable expression persisting for at least 19 months from a single application. Secreted proteins produced in the lung were released into the circulation and stable expression was detectable in blood. The levels of hFVIII in murine blood approached therapeutically relevant targets. rSIV.F/HN was also able to produce secreted hAAT and hFVIII in transduced human primary airway cells. rSIV.F/HN transduction of the murine lungs leads to long-lasting and therapeutically relevant levels of secreted proteins in the lung and systemic circulation. These data broaden the use of this vector platform for a large range of disease indications.

Indexed as

AnimalsDNA, ComplementaryFactor VIIIGenes, ReporterGenetic TherapyGenetic VectorsGene Transfer TechniquesHN ProteinHumansLentivirus InfectionsLungMiceProtein Translocation SystemsSendai virusTransduction, GeneticTransfectionDNA, ComplementaryF8 protein, humanFactor VIIIHN ProteinProtein Translocation SystemsViral Fusion Proteins

Identifiers

PMID30022127
PMCPMC6119181
OpenAlexW2884197373

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.