ArticleNature biotechnology2025
Increasing intracellular dNTP levels improves prime editing efficiency.
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Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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Who cites it
22 citing papers in PubMed.
- Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design.Biodesign research · 2026Review
- Development of a highly efficient prime editing platform for cucurbits enables breeding of multi-disease-resistant cucumber.Journal of integrative plant biology · 2026Article
- Multichannel genomic recording of biological information with ENGRAM.Nature protocols · 2026Review
- Article
- Efficient prime editing in vivo and in vitro using lipid nanoparticles.Nature nanotechnology · 2026Article
- Retargeted serine integrases for one-step, precise integration of large DNA sequences in human cells.Nature biotechnology · 2026Article
- A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Directed evolution of small RNA-stabilizing motifs that improve prime-editing efficiency.Nature biotechnology · 2026Article
- Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026Review
- mRNA-engineered CRISPR-Cas epigenetic editors enable durable and efficient gene silencingInnovation (Cambridge (Mass.)) · 2026Article
- Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Anti-CRISPR protein AcrIIA5 can enhance the activity and security of prime editing.Nature communications · 2025Article
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
- Treatment of a metabolic liver disease in mice with a transient prime editing approach.Nature biomedical engineering · 2025Article
- Article
- Recent advances in therapeutic gene-editing technologies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Modified pegRNAs mitigate scaffold-derived prime editing by-products.Nature communications · 2025Article
- The therapeutic potential of circular RNAs.Nature reviews. Genetics · 2025Review
- Prime Editing: A Revolutionary Technology for Precise Treatment of Genetic Disorders.Cell proliferation · 2025Review
- Increasing intracellular dNTP levels improves prime editing efficiency.Nature biotechnology · 2025Article
Corrections and comments
- Update of
Authors and funding
23 authors.
Pengpeng Liu *Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-4891-8780
Karthikeyan Ponnienselvan *Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-8016-9433
Thomas NyalileProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Sarah OikemusDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Anya T JoyntDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Sukanya IyerDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Karen KellyRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Dongsheng GuoDepartment of Neurology, Wellstone Program, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Pyae P KyaweDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Emma VanderleedenDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0009-0005-5339-1863
Sambra D RedickProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Lei HuangDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-0568-0645
Zexiang ChenRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-1584-2417
Jeong Min LeeDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Celia A SchifferDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-2270-6613
David M HarlanDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Jennifer P WangDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-2556-9100
Charles P EmersonDepartment of Neurology, Wellstone Program, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nathan D LawsonDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Jonathan K WattsRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-5706-1734
Erik J SontheimerProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-0881-0310
Jeremy LubanProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-5650-4054
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. scot.wolfe@umassmed.edu.ORCID http://orcid.org/0000-0002-7042-201X
Funding
CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral DynamicsU54AI170856 · NIAID · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI WALTHER H MOTHES · 2022 to 2026
$34.4MMyogenesis Studies for FSHD BiomarkersU54HD060848 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI EMERSON, CHARLES P. · 2008 to 2017
$16.1MThe HUSH complex in HIV-1 latencyR37AI147868 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI JEREMY LUBAN · 2019 to 2026
$6.4MEmbryonic origins of endothelial heterogeneityR35HL140017 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LAWSON, NATHAN D · 2018 to 2023
$6.0MNext-generation antisense therapeutics for ALS and frontotemporal dementiaR01NS111990 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Robert H Brown, Jonathan K Watts · 2019 to 2026
$5.2MStructurally dissecting APOBEC3's for HIV-1 restriction and beyondR01AI150478 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHIFFER, CELIA A. · 2019 to 2024
$3.9MRectifying splicing mutations in blood disorders by gene editingR01HL150669 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN, WOLFE, SCOT A · 2020 to 2023
$3.5MEnhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUH3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2021 to 2022
$3.1MChemotherapy-free cure of hemoglobin disorders through base editingR01HL170629 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Daniel Evan Bauer, Pietro Genovese · 2023 to 2026
$3.1MIn vivo prime editing for precision cancer mouse modelsR01CA275945 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Wen Xue · 2023 to 2026
$2.5MEnhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUG3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2018 to 2020
$2.5MAdvanced Delivery Platforms for Base Editing In VivoR01GM150273 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ERIK J. SONTHEIMER, Wen Xue · 2023 to 2026
$2.4MJDRF COE-2020-967-M-NNCATS NIH HHS UG3 TR002668NCATS NIH HHS UH3 TR002668NCI NIH HHS R01 CA275945NHLBI NIH HHS R01 HL150669NHLBI NIH HHS R01 HL170629NHLBI NIH HHS R35 HL140017NIAID NIH HHS R01 AI150478NIAID NIH HHS R37 AI147868NIAID NIH HHS U54 AI170856NICHD NIH HHS U54 HD060848NIGMS NIH HHS R01 GM150273NIH HHS R21 OD030004NINDS NIH HHS R01 NS111990U.S. Department of Health & Human Services | National Institutes of Health (NIH) R21OD030004U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U54HD0060848U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) UH3TR002668U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL150669U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R35HL140017U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI150478U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R37AI147868U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U54AI170856U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM150273
Abstract
In primary cell types, intracellular deoxynucleotide triphosphate (dNTP) levels are tightly regulated in a cell cycle-dependent manner. We report that prime editing efficiency is increased by mutations that improve the enzymatic properties of Moloney murine leukemia virus reverse transcriptase and treatments that increase intracellular dNTP levels. In combination, these modifications produce substantial increases in precise editing rates.
Indexed as
DeoxyribonucleotidesGene EditingRNA-Directed DNA PolymeraseAnimalsHumansMiceMoloney murine leukemia virusMutationDeoxyribonucleotidesRNA-Directed DNA Polymerase
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