Evidence map›Paper›PMID 31465962›Full record

ArticleMolecular therapy. Nucleic acids2019

CRISPR-Cas9-Mediated Genome Editing Increases Lifespan and Improves Motor Deficits in a Huntington's Disease Mouse Model.

Freja K Ekman, David S Ojala, Maroof M Adil, Paola A Lopez, David V Schaffer, Thomas Gaj

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

Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

94 citing papers in PubMed, 150 citations in OpenAlex.

  1. Chemically modified CRISPR enzymes for multi-organ genome editingbioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
  4. Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

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

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

6 authors at 2 institutions in 1 country.

Freja K EkmanDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
David S OjalaDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
Maroof M AdilDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
Paola A LopezDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
David V SchafferDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; The Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA. Electronic address: schaffer@berkeley.edu.
Thomas GajDepartment of Bioengineering, University of Illinois, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, IL, USA. Electronic address: gaj@illinois.edu.
University of California, Berkeley · USUniversity of Illinois Urbana-Champaign · US

Funding

Directed Evolution of Adeno-Associated Virus for Retinal Gene TherapyR01EY022975 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI FLANNERY, JOHN GERARD, SCHAFFER, DAVID V · 2014 to 2018
$2.1M
Therapeutic genome editing for amyotrophic lateral sclerosisF32GM113446 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI GAJ, THOMAS · 2015 to 2017
$125k
NEI NIH HHS R01 EY022975NIGMS NIH HHS F32 GM113446
6 · The paper itself

Abstract

Huntington's disease (HD) is a currently incurable and, ultimately, fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene, which results in the production of a mutant protein that forms inclusions and selectively destroys neurons in the striatum and other adjacent structures. The RNA-guided Cas9 endonuclease from CRISPR-Cas9 systems is a versatile technology for inducing DNA double-strand breaks that can stimulate the introduction of frameshift-inducing mutations and permanently disable mutant gene function. Here, we show that the Cas9 nuclease from Staphylococcus aureus, a small Cas9 ortholog that can be packaged alongside a single guide RNA into a single adeno-associated virus (AAV) vector, can be used to disrupt the expression of the mutant HTT gene in the R6/2 mouse model of HD following its in vivo delivery to the striatum. Specifically, we found that CRISPR-Cas9-mediated disruption of the mutant HTT gene resulted in a ∼50% decrease in neuronal inclusions and significantly improved lifespan and certain motor deficits. These results thus illustrate the potential for CRISPR-Cas9 technology to treat HD and other autosomal dominant neurodegenerative disorders caused by a trinucleotide repeat expansion via in vivo genome editing.

Indexed as

AAVCRISPR-Cas9gene therapygenome editingHuntington’s disease

Identifiers

PMID31465962
PMCPMC6717077
OpenAlexW2963369666

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.