Evidence map›Paper›PMID 21415009›Full record

ArticleNucleic acids research2011

A method to sequence and quantify DNA integration for monitoring outcome in gene therapy.

Troy Brady, Shoshannah L Roth, Nirav Malani, Gary P Wang, Charles C Berry, Philippe Leboulch, Salima Hacein-Bey-Abina, Marina Cavazzana-Calvo, Eirini P Papapetrou, Michel Sadelain and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 71 citations in OpenAlex.

  1. Trial
  2. Trial
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  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Characterizing piggyBat-a transposase for genetic modification of T cells.Molecular therapy. Methods & clinical development · 2022
    Article
  11. Article
  12. Article
  13. A Methodology for Assessing Tumor Clonality of Adult T Cell Leukemia/Lymphoma.Molecular therapy. Methods & clinical development · 2020
    Article
  14. Efficient Nuclease-Directed Integration of Lentivirus Vectors into the Human Ribosomal DNA Locus.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  15. TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  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

12 authors at 5 institutions in 2 countries.

Troy BradyDepartment of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Shoshannah L Roth
Nirav Malani
Gary P Wang
Charles C Berry
Philippe Leboulch
Salima Hacein-Bey-Abina
Marina Cavazzana-Calvo
Eirini P Papapetrou
Michel Sadelain
Harri Savilahti
Frederic D Bushman
University of California, San Diego · USInserm · FRUniversité Paris-Saclay · FRUniversity of Pennsylvania · USAssistance Publique – Hôpitaux de Paris · FR

Funding

Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
Massively Parallel Analysis of Integration in Therapeutic Gene TransferR01AI082020 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2009 to 2018
$3.5M
NIAID NIH HHS AI082020NIAID NIH HHS AI52845
6 · The paper itself

Abstract

Human genetic diseases have been successfully corrected by integration of functional copies of the defective genes into human cells, but in some cases integration of therapeutic vectors has activated proto-oncogenes and contributed to leukemia. For this reason, extensive efforts have focused on analyzing integration site populations from patient samples, but the most commonly used methods for recovering newly integrated DNA suffer from severe recovery biases. Here, we show that a new method based on phage Mu transposition in vitro allows convenient and consistent recovery of integration site sequences in a form that can be analyzed directly using DNA barcoding and pyrosequencing. The method also allows simple estimation of the relative abundance of gene-modified cells from human gene therapy subjects, which has previously been lacking but is crucial for detecting expansion of cell clones that may be a prelude to adverse events.

Indexed as

Gene TargetingGenetic TherapyBacteriophage muCell LineHumansPolymerase Chain ReactionSequence Analysis, DNA

Identifiers

PMID21415009
PMCPMC3113588
OpenAlexW2159298101

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.