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Increasing intracellular dNTP levels improves prime editing efficiency.
Liu, Pengpeng; Ponnienselvan, Karthikeyan; Nyalile, Thomas; Oikemus, Sarah; Joynt, Anya T; Iyer, Sukanya; Kelly, Karen; Guo, Dongsheng; Kyawe, Pyae P; Vanderleeden, Emma; Redick, Sambra D; Huang, Lei; Chen, Zexiang; Lee, Jeong Min; Schiffer, Celia A; Harlan, David M; Wang, Jennifer P; Emerson, Charles P; Lawson, Nathan D; Watts, Jonathan K; Sontheimer, Erik J; Luban, Jeremy; Wolfe, Scot A.
Affiliation
  • Liu P; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Ponnienselvan K; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Nyalile T; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Oikemus S; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Joynt AT; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Iyer S; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Kelly K; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Guo D; Department of Neurology, Wellstone Program, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Kyawe PP; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Vanderleeden E; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Redick SD; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Huang L; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Chen Z; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Lee JM; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Schiffer CA; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Harlan DM; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Wang JP; Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Emerson CP; Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Lawson ND; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Watts JK; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Sontheimer EJ; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Luban J; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Wolfe SA; Department of Neurology, Wellstone Program, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nat Biotechnol ; 2024 Sep 25.
Article in En | MEDLINE | ID: mdl-39322763
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Biotechnol Journal subject: BIOTECNOLOGIA Year: 2024 Document type: Article Affiliation country: Estados Unidos Country of publication: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Biotechnol Journal subject: BIOTECNOLOGIA Year: 2024 Document type: Article Affiliation country: Estados Unidos Country of publication: Estados Unidos