Evidence map›Paper›PMID 26444081›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.

Li B Li, Chao Ma, Geneve Awong, Marion Kennedy, German Gornalusse, Gordon Keller, Dan S Kaufman, David W Russell

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  3. Review
  4. Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  5. 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 at 5 institutions in 2 countries.

Li B LiDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Chao MaCollege of Veterinary Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Geneve AwongMcEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
Marion KennedyMcEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
German GornalusseDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Gordon KellerMcEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
Dan S KaufmanDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
David W RussellDepartment of Medicine, University of Washington, Seattle, Washington, USA.
University of Washington · USUniversity of Minnesota · USPrincess Margaret Cancer Centre · CAUniversity Health Network · CAUniversity of Toronto · CA

Funding

VECTOR CONSTRUCTIONS FOR GENE THERAPY OF SICKLE CELL DISEASEP01HL053750 · NHLBI · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1994 to 2014
$30.4M
Expansion of Cardiac and Hematopoietic Pregenitors by Wnt and NotchU01HL100395 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D, MOON, RANDALL TODD · 2009 to 2015
$8.4M
GENE TARGETING BY VIRAL VECTORSR01DK055759 · NIDDK · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1999 to 2017
$5.8M
Canadian Institutes of Health Research MOP126117NHLBI NIH HHS HL53750NHLBI NIH HHS P01 HL053750NHLBI NIH HHS U01 HL100395NHLBI NIH HHS U01HL100395NIDDK NIH HHS DK55759NIDDK NIH HHS R01 DK055759
6 · The paper itself

Abstract

Many applications of pluripotent stem cells (PSCs) require efficient editing of silent chromosomal genes. Here, we show that a major limitation in isolating edited clones is silencing of the selectable marker cassette after homologous recombination and that this can be overcome by using a ubiquitous chromatin opening element (UCOE) promoter-driven transgene. We use this strategy to edit the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus (rAAV)-targeting vector in the absence of potentially genotoxic, site-specific nucleases and show that IL2RG is required for natural killer and T-cell differentiation of human PSCs. Insertion of an active UCOE promoter into a silent locus altered the histone modification and cytosine methylation pattern of surrounding chromatin, but these changes resolved when the UCOE promoter was removed. This same approach could be used to correct IL2RG mutations in X-linked severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent graft versus host disease in regenerative medicine applications, or to edit other silent genes.

Indexed as

Gene EditingGene SilencingCell DifferentiationCell SurvivalCollagen Type ICollagen Type I, alpha 1 ChainEpigenesis, GeneticGene Knockout TechniquesGene TargetingGenetic LociHumansInterleukin Receptor Common gamma SubunitKiller Cells, NaturalPluripotent Stem CellsPromoter Regions, GeneticT-Lymphocyte SubsetsCollagen Type ICollagen Type I, alpha 1 ChainIL2RG protein, humanInterleukin Receptor Common gamma Subunit

Identifiers

PMID26444081
PMCPMC4786911
OpenAlexW2208298605

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.