Evidence map›Paper›PMID 22334016›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012

Alpharetroviral self-inactivating vectors: long-term transgene expression in murine hematopoietic cells and low genotoxicity.

Julia D Suerth, Tobias Maetzig, Martijn H Brugman, Niels Heinz, Jens-Uwe Appelt, Kerstin B Kaufmann, Manfred Schmidt, Manuel Grez, Ute Modlich, Christopher Baum and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. A Hot Topic: Cancer Immunotherapy and Natural Killer Cells.International journal of molecular sciences · 2022
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. An Overview of Methods and Tools for Transfection of Eukaryotic CellsFrontiers in bioengineering and biotechnology · 2021
    Review
  14. Review
  15. Toward Combined Cell and Gene Therapy for Genodermatoses.Cold Spring Harbor perspectives in biology · 2020
    Review
  16. Article
  17. Article
  18. Article
  19. CAR-Expressing Natural Killer Cells for Cancer Retargeting.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2019
    Review
  20. 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

11 authors at 5 institutions in 2 countries.

Julia D SuerthInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Tobias Maetzig
Martijn H Brugman
Niels Heinz
Jens-Uwe Appelt
Kerstin B Kaufmann
Manfred Schmidt
Manuel Grez
Ute Modlich
Christopher Baum
Axel Schambach
Medizinische Hochschule Hannover · DEGeorg Speyer Haus · DEHeidelberg University · DELeiden University Medical Center · NLNational Center for Tumor Diseases · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Comparative integrome analyses have highlighted alpharetroviral vectors with a relatively neutral, and thus favorable, integration spectrum. However, previous studies used alpharetroviral vectors harboring viral coding sequences and intact long-terminal repeats (LTRs). We recently developed self-inactivating (SIN) alpharetroviral vectors with an advanced split-packaging design. In a murine bone marrow (BM) transplantation model we now compared alpharetroviral, gammaretroviral, and lentiviral SIN vectors and showed that all vectors transduced hematopoietic stem cells (HSCs), leading to comparable, sustained multilineage transgene expression in primary and secondary transplanted mice. Alpharetroviral integrations were decreased near transcription start sites, CpG islands, and potential cancer genes compared with gammaretroviral, and decreased in genes compared with lentiviral integrations. Analyzing the transcriptome and intragenic integrations in engrafting cells, we observed stronger correlations between in-gene integration targeting and transcriptional activity for gammaretroviral and lentiviral vectors than for alpharetroviral vectors. Importantly, the relatively "extragenic" alpharetroviral integration pattern still supported long-term transgene expression upon serial transplantation. Furthermore, sensitive genotoxicity studies revealed a decreased immortalization incidence compared with gammaretroviral and lentiviral SIN vectors. We conclude that alpharetroviral SIN vectors have a favorable integration pattern which lowers the risk of insertional mutagenesis while supporting long-term transgene expression in the progeny of transplanted HSCs.

Indexed as

Genetic VectorsTransgenesAlpharetrovirusAnimalsCell LineCpG IslandsGammaretrovirusGene TargetingHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansLentivirusMiceMutagenesis, InsertionalRisk FactorsTerminal Repeat Sequences

Identifiers

PMID22334016
PMCPMC3345992
OpenAlexW2062167821

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.