Evidence map›Paper›PMID 28803727›Full record

ArticleCell2017

Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9.

Ranjan Batra, David A Nelles, Elaine Pirie, Steven M Blue, Ryan J Marina, Harrison Wang, Isaac A Chaim, James D Thomas, Nigel Zhang, Vu Nguyen and 6 more

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

Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 1 pooled it
15.5field-weighted citation impact, top 1% 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

144 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. A pothole-filling strategy for selective targeting of rCUG-repeats associated with myotonic dystrophy type 1.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Review
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  18. Article
  19. Article
  20. Deconstructing cancer with precision genome editing.Biochemical Society transactions · 2024
    Review

84 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Ranjan BatraDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
David A NellesDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Elaine PirieDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Steven M BlueDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Ryan J MarinaDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Harrison WangDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Isaac A ChaimDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
James D ThomasDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.
Nigel ZhangDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Vu NguyenDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Stefan AignerDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Sebastian MarkmillerDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Guangbin XiaDepartment of Neurology, University of Florida, College of Medicine, Gainesville, FL, USA.
Kevin D CorbettDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, CA, USA; Department of Chemistry, University of California, San Diego, La Jolla, CA, USA.
Maurice S SwansonDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Stem Cell Program, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA; Molecular Engineering Laboratory, A(∗)STAR, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: geneyeo@ucsd.edu.
University of California San Diego · USUniversity of Florida · USAgency for Science, Technology and Research · SG

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
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
Defining the messenger RNP code in the brainR01NS075449 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YEO, EUGENE WEI-MING · 2012 to 2016
$3.0M
NHGRI NIH HHS R01 HG004659NIGMS NIH HHS K12 GM068524NIGMS NIH HHS T32 GM008666NINDS NIH HHS R01 NS075449NINDS NIH HHS R01 NS103172
6 · The paper itself

Abstract

Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington's disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for diagnostic and therapeutic purposes. Here, we describe the development of a programmable CRISPR system capable of specifically visualizing and eliminating these toxic RNAs. We observe specific targeting and efficient elimination of microsatellite repeat expansion RNAs both when exogenously expressed and in patient cells. Importantly, RNA-targeting Cas9 (RCas9) reverses hallmark features of disease including elimination of RNA foci among all conditions studied (DM1, DM2, C9-ALS, polyglutamine diseases), reduction of polyglutamine protein products, relocalization of repeat-bound proteins to resemble healthy controls, and efficient reversal of DM1-associated splicing abnormalities in patient myotubes. Finally, we report a truncated RCas9 system compatible with adeno-associated viral packaging. This effort highlights the potential of RCas9 for human therapeutics.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsAnimalsCell LineCells, CulturedChlorocebus aethiopsCOS CellsGenetic TherapyMicrosatellite RepeatsOligonucleotides, AntisenseRNA SplicingTrinucleotide Repeat ExpansionOligonucleotides, Antisenseadeno-associated virusALSCRISPRgene therapyHuntington’s diseasemicrosatellite repeat expansionminimal Cas9myotonic dystrophyRNA-targeting Cas9

Identifiers

PMID28803727
PMCPMC5873302
OpenAlexW2742741050

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.