Evidence map›Paper›PMID 24956106›Full record

ArticlePloS one2014

Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

Nicolas Grandchamp, Dorothée Altémir, Stéphanie Philippe, Suzanna Ursulet, Héloïse Pilet, Marie-Claude Serre, Aude Lenain, Che Serguera, Jacques Mallet, Chamsy Sarkis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
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  4. Review
  5. 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

10 authors at 4 institutions in 1 country.

Nicolas GrandchampUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France; NewVectys, Villebon-sur-Yvette, France; Biosource, Paris, France.
Dorothée AltémirUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France; NewVectys, Villebon-sur-Yvette, France.
Stéphanie PhilippeUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France; NewVectys, Villebon-sur-Yvette, France; Biosource, Paris, France.
Suzanna UrsuletUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France; NewVectys, Villebon-sur-Yvette, France; Biosource, Paris, France.
Héloïse PiletUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France; NewVectys, Villebon-sur-Yvette, France; Biosource, Paris, France.
Marie-Claude SerreLaboratoire de Virologie Moléculaire et Structurale, Gif-sur-Yvette, France.
Aude LenainCommissariat à l'Energie Atomique, Laboratoire de Radiobiologie et Oncologie, Fontenay-aux-Roses, France.
Che SergueraMolecular Imaging Research Center - Modélisation des biothérapies, Fontenay-aux-Roses, France.
Jacques MalletUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France.
Chamsy SarkisUnit of Biotechnology and Biotherapy, Centre de recherche de l'Institut du Cerveau et de la Moelle Epinière, Pierre-and-Marie-Curie University/Institut National de la Santé et de la Recherche Médicale, Paris, France; NewVectys, Villebon-sur-Yvette, France.
Sorbonne Université · FRInstitut du Cerveau · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRLaboratoire de Virologie Moléculaire et Structurale · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV) is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs) solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int) which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP) which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

Indexed as

DNA DamageHybridization, GeneticRecombination, GeneticAnimalsAttachment Sites, MicrobiologicalBacteriophagesBase SequenceCell LineGenetic VectorsHumansLentivirusMiceModels, BiologicalMolecular Sequence DataMutagenesis, InsertionalNuclear Localization SignalsNuclear Localization Signals

Identifiers

PMID24956106
PMCPMC4067480
OpenAlexW1983795781

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.