Evidence map›Paper›PMID 25231175›Full record

ArticleGene therapy2014

High-throughput screening identifies compounds that enhance lentiviral transduction.

J M Johnston, G Denning, R Moot, D Whitehead, J Shields, J M Le Doux, C B Doering, H T Spencer

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Target-Cell-Directed Bioengineering Approaches for Gene Therapy of Hemophilia A.Molecular therapy. Methods & clinical development · 2018
    Article
  12. Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
  13. Article
  14. Article
  15. 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

8 authors.

J M Johnston1] Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA [2] Graduate Program in Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA, USA.
G DenningExpression Therapeutics, LLC, Tucker, GA, USA.
R Moot1] Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA [2] Graduate Program in Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA, USA.
D WhiteheadAflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
J ShieldsAflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
J M Le DouxWallace H Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA, USA.
C B DoeringAflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
H T SpencerAflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A difficulty in the field of gene therapy is the need to increase the susceptibility of hematopoietic stem cells (HSCs) to ex vivo genetic manipulation. To overcome this obstacle a high-throughput screen was performed to identify compounds that could enhance the transduction of target cells by lentiviral vectors. Of the 1280 compounds initially screened using the myeloid-erythroid-leukemic K562 cell line, 30 were identified as possible enhancers of viral transduction. Among the positive hits were known enhancers of transduction (camptothecin, etoposide and taxol), as well as the previously unidentified phorbol 12-myristate 13-acetate (PMA). The percentage of green fluorescent protein (GFP)-positive-expressing K562 cells was increased more than fourfold in the presence of PMA. In addition, the transduction of K562 cells with a lentiviral vector encoding fVIII was four times greater in the presence of PMA as determined by an increase in the levels of provirus in genetically modified cells. PMA did not enhance viral transduction of all cell types (for example, sca-1(+) mouse hematopoietic cells) but did enhance viral transduction of human bone marrow-derived CD34(+) cells. Notably, the percentage of GFP-positive CD34(+) cells was increased from 7% in the absence of PMA to greater than 22% in the presence of 1 nM PMA. PMA did not affect colony formation of CD34(+) cells or the expression of the hematopoietic markers CD34 and CD45. These data demonstrate that high-throughput screening can be used to identify compounds that increase the transduction efficiency of lentiviral vectors, identifying PMA as a potential enhancer of lentiviral HSC transduction.

Indexed as

Transduction, GeneticAnimalsAntigens, CD34CamptothecinCell Line, TumorColforsinGenetic TherapyGenetic VectorsGreen Fluorescent ProteinsHEK293 CellsHematopoietic Stem CellsHigh-Throughput Screening AssaysHumansLentivirusMiceNIH 3T3 CellsAntigens, CD34CamptothecinColforsinGreen Fluorescent Proteinsphorbolol myristate acetateSirolimusTetradecanoylphorbol Acetate

Identifiers

PMID25231175

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.