Evidence map›Paper›PMID 38979269›Full record

ArticlebioRxiv : the preprint server for biology2025

Neuronal DNA repair reveals strategies to influence CRISPR editing outcomes.

Gokul N Ramadoss, Samali J Namaganda, Jennifer R Hamilton, Rohit Sharma, Karena G Chow, Bria L Macklin, Mengyuan Sun, Jia-Cheng Liu, Christof Fellmann, Hannah L Watry and 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Gokul N RamadossGladstone Institutes, San Francisco, CA, 94158, USA.ORCID 0000-0002-7506-2711
Samali J NamagandaGladstone Institutes, San Francisco, CA, 94158, USA.
Jennifer R HamiltonInnovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
Rohit SharmaInnovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
Karena G ChowGladstone Institutes, San Francisco, CA, 94158, USA.
Bria L MacklinGladstone Institutes, San Francisco, CA, 94158, USA.
Mengyuan SunGladstone Institutes, San Francisco, CA, 94158, USA.
Jia-Cheng LiuLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Christof FellmannGladstone Institutes, San Francisco, CA, 94158, USA.
Hannah L WatryGladstone Institutes, San Francisco, CA, 94158, USA.
Julianne JinInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, 94158, USA.
Barbara S PerezInnovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
Cindy R Sandoval EspinozaInnovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
Madeline P MatiaGladstone Institutes, San Francisco, CA, 94158, USA.
Serena H LuGladstone Institutes, San Francisco, CA, 94158, USA.
Luke M JudgeGladstone Institutes, San Francisco, CA, 94158, USA.
Andre NussenzweigLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Britt AdamsonDepartment of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
Niren MurthyInnovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
Jennifer A DoudnaGladstone Institutes, San Francisco, CA, 94158, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, 94158, USA.ORCID 0000-0002-3819-7019
Bruce R ConklinGladstone Institutes, San Francisco, CA, 94158, USA.

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$103.4M
Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 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 CONKLIN, BRUCE R · 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
C9orf72 frontotemporal dementia (FTD) and amyotrophic lateral sclerosis(ALS): using patient cells and CRISPR to reveal therapeutic approachesRF1AG072052 · NIA · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2021 to 2022
$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
NCI NIH HHS HHSN261201500003INHLBI 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 AG072052NIA NIH HHS RF1 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, which must withstand decades of DNA damage without replicating. This lack of knowledge limits the efficiency and precision of genome editing in clinically relevant cells. To address this, we used induced pluripotent stem cells (iPSCs) and iPSC-derived neurons to examine how postmitotic human neurons repair Cas9-induced DNA damage. We discovered that neurons can take weeks to fully resolve this damage, compared to just days in isogenic iPSCs. Furthermore, Cas9-treated neurons upregulated unexpected DNA repair genes, including factors canonically associated with replication. Manipulating this response with chemical or genetic perturbations allowed us to direct neuronal repair toward desired editing outcomes. By studying DNA repair in postmitotic human cells, we uncovered unforeseen challenges and opportunities for precise therapeutic editing.

Identifiers

PMID38979269
PMCPMC11230251

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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.