Evidence map›Paper›PMID 25702800›Full record

ArticleStem cells (Dayton, Ohio)2015

Genome modification leads to phenotype reversal in human myotonic dystrophy type 1 induced pluripotent stem cell-derived neural stem cells.

Guangbin Xia, Yuanzheng Gao, Shouguang Jin, S H Subramony, Naohiro Terada, Laura P W Ranum, Maurice S Swanson, Tetsuo Ashizawa

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

Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 56 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Review
  6. Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Review
  9. Neuromuscular Development and Disease: Learning FromFrontiers in cell and developmental biology · 2021
    Review
  10. Application of CRISPR-Cas9-Mediated Genome Editing for the Treatment of Myotonic Dystrophy Type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Review
  11. Article
  12. Review
  13. DNA repair fidelity in stem cell maintenance, health, and disease.Biochimica et biophysica acta. Molecular basis of disease · 2020
    Review
  14. Article
  15. CRISPR/Cas Applications in Myotonic Dystrophy: Expanding Opportunities.International journal of molecular sciences · 2019
    Review
  16. Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019
    Article
  17. Review
  18. Therapeutic Genome Editing for Myotonic Dystrophy Type 1 Using CRISPR/Cas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  19. Myotonic Dystrophies: Targeting Therapies for Multisystem Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018
    Review
  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

8 authors at 1 institution in 1 country.

Guangbin XiaDepartment of Neurology, University of Florida, College of Medicine, Gainesville, Florida, USA.
Yuanzheng GaoDepartment of Neurology, University of Florida, College of Medicine, Gainesville, Florida, USA.
Shouguang JinDepartment of Molecular Genetics and Microbiology, College of Medicine, Gainesville, Florida, USA.
S H SubramonyDepartment of Neurology, University of Florida, College of Medicine, Gainesville, Florida, USA.
Naohiro TeradaCenter for Cellular Reprogramming, University of Florida, College of Medicine, Gainesville, Florida, USA.
Laura P W RanumDepartment of Neurology, University of Florida, College of Medicine, Gainesville, Florida, USA.
Maurice S SwansonCenter for NeuroGenetics, University of Florida, College of Medicine, Gainesville, Florida, USA.
Tetsuo AshizawaDepartment of Neurology, University of Florida, College of Medicine, Gainesville, Florida, USA.
Florida College · US

Funding

Temporal/spatial RNA Expression Effects in DM1 and DM2P01NS058901 · NINDS · UNIVERSITY OF MINNESOTA · PI RANUM, LAURA P.W · 2008 to 2017
$12.3M
Genome correction of Myotonic Dystrophy type 1 iPS cells by TALEN technologyK08AR064836 · NIAMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI XIA, GUANGBIN · 2013 to 2017
$669k
NIAMS NIH HHS K08 AR064836NIAMS NIH HHS K08 AR064836-01NINDS NIH HHS P01 NS058901
6 · The paper itself

Abstract

Myotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in the 3'-untranslated region (3' UTR) of the DMPK gene. Correcting the mutation in DM1 stem cells would be an important step toward autologous stem cell therapy. The objective of this study is to demonstrate in vitro genome editing to prevent production of toxic mutant transcripts and reverse phenotypes in DM1 stem cells. Genome editing was performed in DM1 neural stem cells (NSCs) derived from human DM1 induced pluripotent stem (iPS) cells. An editing cassette containing SV40/bGH polyA signals was integrated upstream of the CTG repeats by TALEN-mediated homologous recombination (HR). The expression of mutant CUG repeats transcript was monitored by nuclear RNA foci, the molecular hallmarks of DM1, using RNA fluorescence in situ hybridization. Alternative splicing of microtubule-associated protein tau (MAPT) and muscleblind-like (MBNL) proteins were analyzed to further monitor the phenotype reversal after genome modification. The cassette was successfully inserted into DMPK intron 9 and this genomic modification led to complete disappearance of nuclear RNA foci. MAPT and MBNL 1, 2 aberrant splicing in DM1 NSCs were reversed to normal pattern in genome-modified NSCs. Genome modification by integration of exogenous polyA signals upstream of the DMPK CTG repeat expansion prevents the production of toxic RNA and leads to phenotype reversal in human DM1 iPS-cells derived stem cells. Our data provide proof-of-principle evidence that genome modification may be used to generate genetically modified progenitor cells as a first step toward autologous cell transfer therapy for DM1.

Indexed as

Genome, HumanHumansInduced Pluripotent Stem CellsMicrotubule-Associated ProteinsMyotonic DystrophyNeural Stem CellsPhenotypePluripotent Stem CellsMicrotubule-Associated ProteinsCell transplantationGene targetingGenomicsMuscular dystrophyNeural Stem CellPluripotency

Identifiers

PMID25702800
PMCPMC4441571
OpenAlexW1923658373

What OpenQuestion holds

Textmetadata
LicenceTDM
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.