Evidence map›Paper›PMID 24694534›Full record

ArticleGene therapy2014

Developing a potentially immunologically inert tetracycline-regulatable viral vector for gene therapy in the peripheral nerve.

S A Hoyng, S Gnavi, F de Winter, R Eggers, T Ozawa, A Zaldumbide, R C Hoeben, M J A Malessy, J Verhaagen

Open access · bronzeAbstract read
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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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 42 citations in OpenAlex.

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  11. GDNF Gene Therapy to Repair the Injured Peripheral Nerve.Frontiers in bioengineering and biotechnology · 2020
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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

9 authors at 3 institutions in 3 countries.

S A Hoyng1] Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands [2] Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands.
S Gnavi1] Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands [2] Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
F de Winter1] Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands [2] Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands.
R EggersDepartment of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands.
T OzawaDepartment of Chemistry, School of Science, University of Tokyo, Tokyo, Japan.
A ZaldumbideDepartment of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
R C HoebenDepartment of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
M J A Malessy1] Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands [2] Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands.
J Verhaagen1] Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands [2] Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Royal Netherlands Academy of Arts and Sciences · NLLeiden University Medical Center · NLThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Viral vector-mediated gene transfer of neurotrophic factors is an emerging and promising strategy to promote the regeneration of injured peripheral nerves. Unfortunately, the chronic exposure to neurotrophic factors results in local trapping of regenerating axons or other unwanted side effects. Therefore, tight control of therapeutic gene expression is required. The tetracycline/doxycycline-inducible system is considered to be one of the most promising systems for regulating heterologous gene expression. However, an immune response directed against the transactivator protein rtTA hampers further translational studies. Immunogenic proteins fused with the Gly-Ala repeat of the Epstein-Barr virus Nuclear Antigen-1 protein have been shown to successfully evade the immune system. In this article, we used this strategy to demonstrate that a chimeric transactivator, created by fusing the Gly-Ala repeat with rtTA and embedded in a lentiviral vector (i) retained its transactivator function in vitro, in muscle explants, and in vivo following injection into the rat peripheral nerve, (ii) exhibited a reduced leaky expression, and (iii) had an immune-evasive advantage over rtTA as shown in a novel bioassay for human antigen presentation. The current findings are an important step toward creating a clinically applicable potentially immune-evasive tetracycline-regulatable viral vector system.

Indexed as

AnimalsBase SequenceFemaleGene Expression RegulationGenetic TherapyGenetic VectorsHEK293 CellsHumansIn Vitro TechniquesLentivirusMolecular Sequence DataMuscle, SkeletalPeripheral NervesRats, WistarTetracyclineT-Lymphocytes, CytotoxicTetracyclineTrans-Activators

Identifiers

PMID24694534
OpenAlexW2059005277

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.