Evidence map›Paper›PMID 25605795›Full record

ArticleNucleic acids research2015

Evaluating the potential for undesired genomic effects of the piggyBac transposon system in human cells.

Sunandan Saha, Lauren E Woodard, Elizabeth M Charron, Richard C Welch, Cliona M Rooney, Matthew H Wilson

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05054257 (Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells), which is not on this map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-weighted citation impact, top 9% 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.

NCT05054257 phase1recruitingnot on this mapstarted 2021, after this paper: background citation

Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells (CART19) in Patients with Relapsed/refractory CD19+ Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma. a Dose Escalation, Open-label, Phase I Study.

TypeinterventionalSponsorInstitute of Hematology and Blood Transfusion, Czech RepublicRan2021 to 2025Enrolled10ConditionsRelapsed or Refractory B-cell Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma Refractory, Non-Hodgkin's Lymphoma, RelapsedArmsAutologous CAR19 T lymphocytes
3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  3. Stargardt macular dystrophy and therapeutic approaches.The British journal of ophthalmology · 2024
    Review
  4. Review
  5. Response to: DNA transposon mechanisms and pathways of genotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  6. DNA transposon mechanisms and pathways of genotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  7. ASIS-Seq: Transgene Insertion Site Mapping by Nanopore Adaptive Sampling.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Applications ofStem cells international · 2021
    Review
  13. Genome Engineering of Yarrowia lipolytica with the PiggyBac Transposon System.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  14. Article
  15. Cellular and metabolic engineering of oleaginous yeastEngineering in life sciences · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

6 authors at 1 institution in 1 country.

Sunandan SahaDepartment of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Lauren E WoodardDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Elizabeth M CharronDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Richard C WelchDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Cliona M RooneyInterdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Matthew H WilsonInterdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA matthew.wilson@vanderbilt.edu.
Baylor College of Medicine · US

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
Virology CoreP30AI036211 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI RICE, ANDREW P · 1994 to 2015
$21.7M
Novel cell therapy for sustained therapeutic protein delivery in vivoR01DK093660 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, MATTHEW H · 2012 to 2022
$3.4M
BD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430k
Kidney specific site-directed integration for cystinuriaI01BX002190 · VA · VETERANS HEALTH ADMINISTRATION · PI WILSON, MATTHEW H · 2014 to 2017
–
In Situ Reprogramming of Induced Nephron Progenitor Cells for Kidney RegenerationIK2BX002797 · VA · VETERANS HEALTH ADMINISTRATION · PI WOODARD, LAUREN ELIZABETH · 2015 to 2020
–
BLRD VA I01 BX002190BLRD VA IK2 BX002797Howard Hughes Medical InstituteNCI NIH HHS P30CA125123NCRR NIH HHS S10RR024574NIAID NIH HHS P30AI036211NIDDK NIH HHS DK093660NIDDK NIH HHS R01 DK093660
6 · The paper itself

Abstract

Non-viral transposons have been used successfully for genetic modification of clinically relevant cells including embryonic stem, induced pluripotent stem, hematopoietic stem and primary human T cell types. However, there has been limited evaluation of undesired genomic effects when using transposons for human genome modification. The prevalence of piggyBac(PB)-like terminal repeat (TR) elements in the human genome raises concerns. We evaluated if there were undesired genomic effects of the PB transposon system to modify human cells. Expression of the transposase alone revealed no mobilization of endogenous PB-like sequences in the human genome and no increase in DNA double-strand breaks. The use of PB in a plasmid containing both transposase and transposon greatly increased the probability of transposase integration; however, using transposon and transposase from separate vectors circumvented this. Placing a eGFP transgene within transposon vector backbone allowed isolation of cells free from vector backbone DNA. We confirmed observable directional promoter activity within the 5'TR element of PB but found no significant enhancer effects from the transposon DNA sequence. Long-term culture of primary human cells modified with eGFP-transposons revealed no selective growth advantage of transposon-harboring cells. PB represents a promising vector system for genetic modification of human cells with limited undesired genomic effects.

Indexed as

Chromosomes, Artificial, BacterialDNA Transposable ElementsGenome, Human5' Untranslated RegionsDNA DamageGreen Fluorescent ProteinsHEK293 CellsHumansPlasmidsPolymerase Chain ReactionTransgenesTransposases5' Untranslated RegionsDNA Transposable Elementsenhanced green fluorescent proteinGreen Fluorescent ProteinsTransposases

Identifiers

PMID25605795
PMCPMC4330379
OpenAlexW2108672655

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.