Evidence map›Paper›PMID 25291142›Full record

ArticleMolecular therapy. Nucleic acids2014

Clonal Dominance With Retroviral Vector Insertions Near the ANGPT1 and ANGPT2 Genes in a Human Xenotransplant Mouse Model.

Reinhard Haemmerle, Ruhi Phaltane, Michael Rothe, Simon Schröder, Axel Schambach, Thomas Moritz, Ute Modlich

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy.Molecular therapy. Methods & clinical development · 2018
    Review
  5. Article
  6. Article
  7. Review
  8. Lentiviral gene therapy using cellular promoters cures type 1 Gaucher disease in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    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

7 authors at 2 institutions in 1 country.

Reinhard Haemmerle1] Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany [2] Research Group Reprogramming and Gene Therapy, Rebirth Cluster-of-Excellence, Hannover Medical School, Hannover, Germany.
Ruhi Phaltane1] Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany [2] Research Group Reprogramming and Gene Therapy, Rebirth Cluster-of-Excellence, Hannover Medical School, Hannover, Germany.
Michael RotheInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Simon SchröderInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Axel SchambachInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Thomas Moritz1] Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany [2] Research Group Reprogramming and Gene Therapy, Rebirth Cluster-of-Excellence, Hannover Medical School, Hannover, Germany.
Ute Modlich1] Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany [2] Research Group for Gene Modification in Stem Cells, LOEWE Centre for Cell and Gene Therapy Frankfurt/Main and the Paul-Ehrlich-Institute, Langen, Germany.
Medizinische Hochschule Hannover · DEPaul Ehrlich Institut · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Insertional leukemogenesis represents the major risk factor of hematopoietic stem cell (HSC) based gene therapy utilizing integrating viral vectors. To develop a pre-clinical model for the evaluation of vector-related genotoxicity directly in the relevant human target cells, cord blood CD34(+) HSCs were transplanted into immunodeficient NOD.SCID.IL2rg(-/-) (NSG) mice after transduction with an LTR-driven gammaretroviral vector (GV). Furthermore, we specifically investigated the effect of prolonged in vitro culture in the presence of cytokines recently described to promote HSC expansion or maintenance. Clonality of human hematopoiesis in NSG mice was assessed by high throughput insertion site analyses and validated by insertion site-specific PCR depicting a GV typical integration profile with insertion sites resembling to 25% those of clinical studies. No overrepresentation of integrations in the vicinity of cancer-related genes was observed, however, several dominant clones were identified including two clones harboring integrations in the ANGPT1 and near the ANGPT2 genes associated with deregulated ANGPT1- and ANGPT2-mRNA levels. While these data underscore the potential value of the NSG model, our studies also identified short-comings such as overall low numbers of engrafted HSCs, limited in vivo observation time, and the challenges of in-depth insertion site analyses by low contribution of gene modified hematopoiesis.

Identifiers

PMID25291142
PMCPMC4217076
OpenAlexW1986154710

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.