Evidence map›Paper›PMID 41249169›Full record

ArticleNature communications2025

Characterizing and controlling CRISPR repair outcomes in nondividing human cells.

Gokul N Ramadoss, Samali J Namaganda, Manasi M Kumar, Jennifer R Hamilton, Rohit Sharma, Karena G Chow, Luke A Workley, Bria L Macklin, Mengyuan Sun, Alvin S Ha and 18 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Haplotype editing with CRISPR-Cas9 as a therapeutic approach for dominant-negative missense mutations in NEFL.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  11. Article
  12. Advances in Therapeutics Research for Demyelinating Diseases.Pharmaceuticals (Basel, Switzerland) · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Gokul N RamadossGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7506-2711
Samali J NamagandaGladstone Institutes, San Francisco, CA, USA.
Manasi M KumarGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0009-0001-8985-7849
Jennifer R HamiltonInnovative Genomics Institute, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-7136-1757
Rohit SharmaInnovative Genomics Institute, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-1428-5521
Karena G ChowGladstone Institutes, San Francisco, CA, USA.
Luke A WorkleyGladstone Institutes, San Francisco, CA, USA.
Bria L MacklinGladstone Institutes, San Francisco, CA, USA.
Mengyuan SunGladstone Institutes, San Francisco, CA, USA.
Alvin S HaGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7092-9072
Jia-Cheng LiuLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.
Christof FellmannGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9545-5723
Hannah L WatryGladstone Institutes, San Francisco, CA, USA.
Philip H DierksGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5903-8343
Rudra S BoseInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Julianne JinInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0009-0008-9877-9716
Barbara S PerezInnovative Genomics Institute, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0009-0001-4619-8919
Cindy R Sandoval EspinozaInnovative Genomics Institute, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-2308-0413
Madeline P MatiaGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4694-8396
Serena H LuGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0434-8840
Luke M JudgeGladstone Institutes, San Francisco, CA, USA.
Brian R ShyGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9569-3708
Andre NussenzweigLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.
Britt AdamsonDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-9451-5819
Niren MurthyInnovative Genomics Institute, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-7815-7337
Jennifer A DoudnaGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9161-999X
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3819-7019
Bruce R ConklinGladstone Institutes, San Francisco, CA, USA. bconklin@gladstone.ucsf.edu.ORCID http://orcid.org/0000-0003-1463-6061

Funding

Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDREJ SALI · 2022 to 2026
$35.7M
HOPE - HIV Obstruction by Programmed EpigeneticsUM1AI164559 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Lishomwa C Ndhlovu, Melanie Maria Ott · 2021 to 2026
$32.2M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4M
Resource Core II: In Vivo CoreU19NS132303 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI NIREN MURTHY · 2023 to 2026
$19.7M
Project 3: Control of cardiac transcription by MEF2 and myocardinP01HL146366 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BLACK, BRIAN L · 2019 to 2023
$13.7M
Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Gene editing in the brain with CRISPR-PEGR01MH125979 · NIMH · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LEE, HYE YOUNG, MURTHY, NIREN · 2021 to 2025
$3.3M
Mapping the DNA damage response in human cells with high-resolution functional genomicsR35GM138167 · NIGMS · PRINCETON UNIVERSITY · PI Brittany S. Adamson · 2020 to 2026
$2.4M
Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systemsU01AI142817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BANFIELD, JILLIAN, DOUDNA, JENNIFER A · 2018 to 2022
$2.0M
Allele-specific inactivation for dominant negative NEFL MutationsR01NS119678 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JUDGE, LUKE M · 2021 to 2025
$1.9M
Identifying Therapeutic Targets for RNA Splicing-Related CardiomyopathyR01HL130533 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2016 to 2019
$1.8M
C9orf72 frontotemporal dementia (FTD) and amyotrophic lateral sclerosis(ALS): using patient cells and CRISPR to reveal therapeutic approachesR01AG072052 · NIA · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2024 to 2025
$1.4M
NCATS NIH HHS L30 TR002983NCI NIH HHS HHSN261201500003INCI NIH HHS K08 CA273529NHLBI NIH HHS P01 HL146366NHLBI NIH HHS R01 HL130533NHLBI NIH HHS R21 HL173710NIAID NIH HHS U01 AI142817NIAID NIH HHS U19 AI135990NIAID NIH HHS U54 AI170792NIAID NIH HHS UH3 AI150552NIAID NIH HHS UM1 AI164559NIA NIH HHS F32 AG081085NIA NIH HHS R01 AG072052NIGMS NIH HHS K99 GM143461NIGMS NIH HHS R00 GM118909NIGMS NIH HHS R35 GM138167NIGMS NIH HHS R35 GM143124NIGMS NIH HHS T32 GM136547NIMH NIH HHS R01 MH125979NINDS NIH HHS R01 NS119678NINDS NIH HHS U19 NS132303
6 · The paper itself

Abstract

Genome editing is poised to revolutionize treatment of genetic diseases, but poor understanding and control of DNA repair outcomes hinders its therapeutic potential. DNA repair is especially understudied in nondividing cells like neurons, limiting the efficiency and precision of genome editing in many clinically relevant tissues. Here, we address this barrier by using induced pluripotent stem cells (iPSCs) and iPSC-derived neurons to examine how postmitotic human neurons repair Cas9-induced DNA damage. CRISPR editing outcomes differ dramatically in neurons compared to genetically identical dividing cells: neurons take longer to fully resolve this damage, and upregulate non-canonical DNA repair factors in the process. Manipulating this response with chemical or genetic perturbations allows us to direct DNA repair toward desired editing outcomes in nondividing human neurons, cardiomyocytes, and primary T cells. By studying DNA repair in clinically relevant cells, we reveal unforeseen challenges and opportunities for precise therapeutic editing.

Indexed as

CRISPR-Cas SystemsDNA RepairGene EditingNeuronsDNA DamageHumansInduced Pluripotent Stem CellsMyocytes, CardiacT-Lymphocytes

Identifiers

PMID41249169
PMCPMC12623481

What OpenQuestion holds

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Registered trials

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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.