Characterizing and controlling CRISPR repair outcomes in nondividing human cells Article Swipe
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
,
Jia-Cheng Liu
,
Christof Fellmann
,
Hannah L. Watry
,
Philip H Dierks
,
Rudra S. Bose
,
Julianne Jin
,
Barbara S. Perez
,
Cindy R. Sandoval Espinoza
,
Madeline P. Matia
,
Serena H Lu
,
Luke M. Judge
,
Brian R. Shy
,
André Nussenzweig
,
Britt Adamson
,
Niren Murthy
,
Jennifer A. Doudna
,
Martin Kampmann
,
Bruce R. Conklin
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-025-66058-3
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-025-66058-3
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.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41467-025-66058-3
- https://www.nature.com/articles/s41467-025-66058-3.pdf
- OA Status
- gold
- References
- 69
- OpenAlex ID
- https://openalex.org/W4416299167
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4416299167Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41467-025-66058-3Digital Object Identifier
- Title
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Characterizing and controlling CRISPR repair outcomes in nondividing human cellsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-11-17Full publication date if available
- Authors
-
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, Jia-Cheng Liu, Christof Fellmann, Hannah L. Watry, Philip H Dierks, Rudra S. Bose, Julianne Jin, Barbara S. Perez, Cindy R. Sandoval Espinoza, Madeline P. Matia, Serena H Lu, Luke M. Judge, Brian R. Shy, André Nussenzweig, Britt Adamson, Niren Murthy, Jennifer A. Doudna, Martin Kampmann, Bruce R. ConklinList of authors in order
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https://doi.org/10.1038/s41467-025-66058-3Publisher landing page
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https://www.nature.com/articles/s41467-025-66058-3.pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.nature.com/articles/s41467-025-66058-3.pdfDirect OA link when available
- Cited by
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0Total citation count in OpenAlex
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69Number of works referenced by this work
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| referenced_works | https://openalex.org/W3006116138, https://openalex.org/W4295427499, https://openalex.org/W4206238555, https://openalex.org/W2050480410, https://openalex.org/W2336828812, https://openalex.org/W2766599608, https://openalex.org/W2981137429, https://openalex.org/W3204978797, https://openalex.org/W3174716159, https://openalex.org/W3206354438, https://openalex.org/W2791875139, https://openalex.org/W2777540887, https://openalex.org/W2963369666, https://openalex.org/W4394804036, https://openalex.org/W2953587283, https://openalex.org/W3195336893, https://openalex.org/W2414247940, https://openalex.org/W4210997735, https://openalex.org/W3139535723, https://openalex.org/W2125644182, https://openalex.org/W4224235324, https://openalex.org/W4283799404, https://openalex.org/W4393219008, https://openalex.org/W2803819386, https://openalex.org/W2967789674, https://openalex.org/W3164457455, https://openalex.org/W4390750892, https://openalex.org/W4206390074, https://openalex.org/W2949383259, https://openalex.org/W2073246940, https://openalex.org/W3127333316, https://openalex.org/W4384154872, https://openalex.org/W2007321086, https://openalex.org/W2995349514, https://openalex.org/W3127347270, https://openalex.org/W2976933625, https://openalex.org/W3012151639, https://openalex.org/W2804348137, https://openalex.org/W4387142572, https://openalex.org/W4297502055, https://openalex.org/W2888718906, https://openalex.org/W2900885456, https://openalex.org/W1969474286, https://openalex.org/W2036546456, https://openalex.org/W3212591340, https://openalex.org/W4293004809, https://openalex.org/W3175390442, https://openalex.org/W2089950231, https://openalex.org/W2920993016, https://openalex.org/W3137019332, https://openalex.org/W2606935752, https://openalex.org/W2026630877, https://openalex.org/W2006277511, https://openalex.org/W3107285902, https://openalex.org/W4376870012, https://openalex.org/W2163173306, https://openalex.org/W2807077922, https://openalex.org/W3033735755, https://openalex.org/W2117278104, https://openalex.org/W2164193797, https://openalex.org/W2981114721, https://openalex.org/W2035105453, https://openalex.org/W2127027122, https://openalex.org/W2964067043, https://openalex.org/W3083295807, https://openalex.org/W3155689026, https://openalex.org/W4396871080, https://openalex.org/W2548694234, https://openalex.org/W4387307597 |
| referenced_works_count | 69 |
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| abstract_inverted_index.By | 129 |
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