Evidence map›Paper›PMID 32929188›Full record

ArticleNature biomedical engineering2021

The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1.

Ranjan Batra, David A Nelles, Daniela M Roth, Florian Krach, Curtis A Nutter, Takahiro Tadokoro, James D Thomas, Łukasz J Sznajder, Steven M Blue, Haydee L Gutierrez and 7 more

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

Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.7field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. 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
  6. Article
  7. Review
  8. Muscular Dystrophies.Advances in experimental medicine and biology · 2025
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. CRISPR-Based Tools for Fighting Rare Diseases.Life (Basel, Switzerland) · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Ranjan Batra *Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
David A Nelles *Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Daniela M RothLocanabio, La Jolla, CA, USA.
Florian KrachDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Curtis A NutterDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.
Takahiro TadokoroDepartment of Anesthesiology, School of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4884-0247
James D ThomasDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-8893-6350
Łukasz J SznajderDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.ORCID http://orcid.org/0000-0001-6822-6485
Steven M BlueDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Haydee L GutierrezLocanabio, La Jolla, CA, USA.
Patrick LiuLocanabio, La Jolla, CA, USA.
Stefan AignerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Oleksandr PlatoshynNeuroregeneration Laboratory, Department of Anesthesiology, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-6529-6752
Atsushi MiyanoharaNeuroregeneration Laboratory, Department of Anesthesiology, University of California San Diego, La Jolla, CA, USA.
Martin MarsalaNeuroregeneration Laboratory, Department of Anesthesiology, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5048-6422
Maurice S SwansonDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.ORCID http://orcid.org/0000-0001-6245-5367
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. geneyeo@ucsd.edu.ORCID http://orcid.org/0000-0002-0799-6037
University of California San Diego · USUniversity of Florida · USLa Jolla Bioengineering Institute · US

Funding

Senator Paul D. Wellstone Muscular Dystrophy Specialized Research CenterP50NS048843 · NINDS · UNIVERSITY OF ROCHESTER · PI THORNTON, CHARLES A · 2018 to 2022
$7.1M
Therapeutic strategies for microsatellite expansion diseases using RNA-targeting CRISPR/CasR01NS103172 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MAURICE SCOTT SWANSON, Eugene Wei-Ming Yeo · 2017 to 2026
$5.6M
NINDS NIH HHS P50 NS048843NINDS NIH HHS R01 NS103172
6 · The paper itself

Abstract

Myotonic dystrophy type I (DM1) is a multisystemic autosomal-dominant inherited human disorder that is caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of DMPK. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated RNA targeting, yet evidence of its in vivo efficacy and durability is lacking. Here, using adult and neonatal mouse models of DM1, we show that intramuscular or systemic injections of adeno-associated virus (AAV) vectors encoding nuclease-dead Cas9 and a single-guide RNA targeting CUG repeats results in the expression of the RNA-targeting Cas9 for up to three months, redistribution of the RNA-splicing protein muscleblind-like splicing regulator 1, elimination of foci of toxic RNA, reversal of splicing biomarkers and amelioration of myotonia. The sustained reversal of DM1 phenotypes provides further support that RNA-targeting Cas9 is a viable strategy for treating DM1 and other MRE-associated diseases.

Indexed as

CRISPR-Cas SystemsAdenoviridaeAnimalsCRISPR-Associated Protein 9Disease Models, AnimalFemaleGene EditingGenetic VectorsMaleMice, TransgenicMuscle, SkeletalMyotonic DystrophyPhenotypeRNACRISPR-Associated Protein 9RNA

Identifiers

PMID32929188
PMCPMC8241012
OpenAlexW3085086432

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.