Evidence map›Paper›PMID 26316390›Full record

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

Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene Targeting in X-linked Chronic Granulomatous Disease iPSCs.

Magdalena Laugsch, Maria Rostovskaya, Sergiy Velychko, Cornelia Richter, Ariane Zimmer, Barbara Klink, Evelin Schröck, Michael Haase, Katrin Neumann, Sebastian Thieme and 3 more

Open access · hybridAbstract 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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Frontiers in immunology · 2022
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. A New Chapter on Targeted Gene Insertion for X-CGD: Do Not Skip the Intro(n).Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
  10. Article
  11. Chronic Granulomatous Disease.Indian journal of pediatrics · 2016
    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

13 authors at 2 institutions in 1 country.

Magdalena LaugschDepartment of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Maria RostovskayaStem Cell Engineering, BIOTEC, TU Dresden, Dresden, Germany.
Sergiy VelychkoStem Cell Engineering, BIOTEC, TU Dresden, Dresden, Germany.
Cornelia RichterDepartment of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Ariane ZimmerDepartment of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Barbara KlinkInstitute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
Evelin SchröckInstitute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
Michael HaaseDepartment of Pediatric Surgery, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Katrin NeumannStem Cell Engineering, BIOTEC, TU Dresden, Dresden, Germany.
Sebastian ThiemeDepartment of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Joachim RoeslerDepartment of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Sebastian BrennerDepartment of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Konstantinos AnastassiadisStem Cell Engineering, BIOTEC, TU Dresden, Dresden, Germany.
TU Dresden · DEUniversity Hospital Carl Gustav Carus · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic granulomatous disease (CGD) is an inherited immunodeficiency, caused by the inability of neutrophils to produce functional NADPH oxidase required for fighting microbial infections. The X-linked form of CGD (X-CGD), which is due to mutations in the CYBB (gp91phox) gene, a component of NADPH oxidase, accounts for about two-thirds of CGD cases. We derived induced pluripotent stem cells (iPSCs) from X-CGD patient keratinocytes using a Flp recombinase excisable lentiviral reprogramming vector. For restoring gp91phox function, we applied two strategies: transposon-mediated bacterial artificial chromosome (BAC) transgenesis and gene targeting using vectors with a fixed 5' homology arm (HA) of 8 kb and 3'HA varying in size from 30 to 80 kb. High efficiency of homologous recombination (up to 22%) was observed with increased size of the 3'HA. Both, BAC transgenesis and gene targeting resulted in functional restoration of the gp91phox measured by an oxidase activity assay in X-CGD iPSCs differentiated into the myeloid lineage. In conclusion, we delivered an important milestone towards the use of genetically corrected autologous cells for the treatment of X-CGD and monogenic diseases in general.

Indexed as

Gene Transfer TechniquesCell DifferentiationCells, CulturedChromosomes, Artificial, BacterialGene TargetingGenetic TherapyGenetic VectorsGranulomatous Disease, ChronicHumansInduced Pluripotent Stem CellsKeratinocytesMembrane GlycoproteinsMutationNADPH Oxidase 2NADPH OxidasesCYBB protein, humanMembrane GlycoproteinsNADPH Oxidase 2NADPH Oxidases

Identifiers

PMID26316390
PMCPMC4886927
OpenAlexW1234938885

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.