Evidence map›Paper›PMID 33171139›Full record

ReviewMolecular therapy : the journal of the American Society of Gene Therapy2020

Application of CRISPR-Cas9-Mediated Genome Editing for the Treatment of Myotonic Dystrophy Type 1.

Seren Marsh, Britt Hanson, Matthew J A Wood, Miguel A Varela, Thomas C Roberts

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

Review in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. 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
1.3field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Myotonic dystrophies: an update on clinical features, molecular mechanisms, management, and gene therapy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024
    Review
  8. Article
  9. Current Strategies of Muscular Dystrophy Therapeutics: An Overview.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  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

5 authors at 1 institution in 1 country.

Seren MarshUniversity of Oxford Medical School, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, UK.
Britt HansonDepartment of Physiology, Anatomy and Genetics, Oxford OX1 3QX, UK; Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK.
Matthew J A WoodDepartment of Paediatrics, University of Oxford, Oxford OX1 3QX, UK; MDUK Oxford Neuromuscular Centre, UK.
Miguel A VarelaDepartment of Paediatrics, University of Oxford, Oxford OX1 3QX, UK.
Thomas C RobertsDepartment of Paediatrics, University of Oxford, Oxford OX1 3QX, UK; MDUK Oxford Neuromuscular Centre, UK. Electronic address: thomas.roberts@paediatrics.ox.ac.uk.
University of Oxford · GB

Funding

Medical Research Council MR/P01741X/1
6 · The paper itself

Abstract

Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder, caused by expansion of a CTG microsatellite repeat in the 3' untranslated region of the DMPK (dystrophia myotonica protein kinase) gene. To date, novel therapeutic approaches have focused on transient suppression of the mutant, repeat-expanded RNA. However, recent developments in the field of genome editing have raised the exciting possibility of inducing permanent correction of the DM1 genetic defect. Specifically, repurposing of the prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system has enabled programmable, site-specific, and multiplex genome editing. CRISPR-based strategies for the treatment of DM1 can be applied either directly to patients, or indirectly through the ex vivo modification of patient-derived cells, and they include excision of the repeat expansion, insertion of synthetic polyadenylation signals upstream of the repeat, steric interference with RNA polymerase II procession through the repeat leading to transcriptional downregulation of DMPK, and direct RNA targeting of the mutant RNA species. Potential obstacles to such therapies are discussed, including the major challenge of Cas9 and guide RNA transgene/ribonuclear protein delivery, off-target gene editing, vector genome insertion at cut sites, on-target unintended mutagenesis (e.g., repeat inversion), pre-existing immunity to Cas9 or AAV antigens, immunogenicity, and Cas9 persistence.

Indexed as

CRISPR-Cas SystemsAnimalsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9DependovirusDisease Models, AnimalGene EditingGenetic TherapyGenetic VectorsHumansMiceMyotonic DystrophyMyotonin-Protein KinaseRNA, Guide, CRISPR-Cas SystemsTreatment OutcomeTrinucleotide Repeat ExpansionCRISPR-Associated Protein 9DMPK protein, humanMyotonin-Protein KinaseRNA, Guide, CRISPR-Cas SystemsAAVCas9CRISPRDM1gene editingmyotonic dystrophy

Identifiers

PMID33171139
PMCPMC7704741
OpenAlexW3093423776

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.