Evidence map›Paper›PMID 37403358›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.

Elizabeth C Stahl, Jennifer K Sabo, Min Hyung Kang, Ryan Allen, Elizabeth Applegate, Shin Eui Kim, Yoonjin Kwon, Anmol Seth, Nicholas Lemus, Viviana Salinas-Rios and 10 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
6.6field-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

23 citing papers in PubMed, 43 citations in OpenAlex.

  1. Chemically modified CRISPR enzymes for multi-organ genome editingbioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Peeling back the layers of immunogenicity in Cas9-based genomic medicine.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  12. Article
  13. Ablation of dysmorphic neurons is a safe and effective treatment for focal cortical dysplasia II.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Temporal and spatial dynamics ofProceedings of the National Academy of Sciences of the United States of America · 2024
    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

20 authors at 4 institutions in 1 country.

Elizabeth C StahlInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Jennifer K SaboInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Min Hyung KangInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Ryan AllenInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Elizabeth ApplegateInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Shin Eui KimInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Yoonjin KwonInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Anmol SethInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Nicholas LemusInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Viviana Salinas-RiosInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Katarzyna M SoczekInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Marena TrinidadInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Linda T VoInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Chris JeansCalifornia Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Anna WozniakAldevron LLC, Madison, WI 53719, USA.
Timothy MorrisAldevron LLC, Madison, WI 53719, USA.
Athen KimberlinAldevron LLC, Madison, WI 53719, USA.
Thomas FotiAldevron LLC, Madison, WI 53719, USA.
David F SavageInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Jennifer A DoudnaInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Gladstone Institutes, University of California, Berkeley, San Francisco, CA 94114, USA. Electronic address: doudna@berkeley.edu.
Innovative Genomics Institute · USAldevron (United States) · USQB3 · USHoward Hughes Medical Institute · US

Funding

Engineering improved delivery and immune profiles of Cas9 orthologues for gene therapyF32GM140637 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI STAHL, ELIZABETH · 2021 to 2022
$124k
NIGMS NIH HHS F32 GM140637
6 · The paper itself

Abstract

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing.

Indexed as

CRISPR-Cas SystemsGene EditingAnimalsBrainCRISPR-Associated Protein 9MiceRibonucleoproteinsCRISPR-Associated Protein 9RibonucleoproteinsbrainCRISPR-Cas9endotoxin/LPSgenome editinghost immune responsemicrogliamouseneuronsnon-viral deliveryviral vectors

Identifiers

PMID37403358
PMCPMC10422012
OpenAlexW4383103732

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.