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Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs.

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Title: Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs.
Authors: Whittaker MN; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Testa LC; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Quigley A; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Brooks DL; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Grandinette SA; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Said H; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Bioengineering, George Mason University, Fairfax, VA, USA., Dwivedi G; Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Jindal I; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Volpp D; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Hacker JL; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Qu P; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Wang JZ; Agilent Technologies Inc., Santa Clara, CA, USA., Levine MA; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Ahrens-Nicklas RC; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Human Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Li Q; Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA.; PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA., Musunuru K; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. kiranmusunuru@gmail.com.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. kiranmusunuru@gmail.com.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. kiranmusunuru@gmail.com.; Division of Human Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA, USA. kiranmusunuru@gmail.com., Alameh MG; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. mg.alameh@pennmedicine.upenn.edu.; Department of Bioengineering, George Mason University, Fairfax, VA, USA. mg.alameh@pennmedicine.upenn.edu.; Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mg.alameh@pennmedicine.upenn.edu.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. mg.alameh@pennmedicine.upenn.edu., Peranteau WH; The Center for Fetal Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA. peranteauw@chop.edu.; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA. peranteauw@chop.edu., Wang X; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. xiao8@pennmedicine.upenn.edu.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. xiao8@pennmedicine.upenn.edu.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. xiao8@pennmedicine.upenn.edu.
Source: Nature biomedical engineering [Nat Biomed Eng] 2025 Oct 28. Date of Electronic Publication: 2025 Oct 28.
Publication Type: Journal Article
Journal Info: Publisher: Springer Nature Country of Publication: England NLM ID: 101696896 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2157-846X (Electronic) Linking ISSN: 2157846X NLM ISO Abbreviation: Nat Biomed Eng Subsets: MEDLINE
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  Data: <searchLink fieldCode="AU" term="%22Whittaker+MN%22">Whittaker MN</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Testa+LC%22">Testa LC</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Quigley+A%22">Quigley A</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Brooks+DL%22">Brooks DL</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Grandinette+SA%22">Grandinette SA</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 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Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Qu+P%22">Qu P</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Wang+JZ%22">Wang JZ</searchLink>; Agilent Technologies Inc., Santa Clara, CA, USA.<br /><searchLink fieldCode="AU" term="%22Levine+MA%22">Levine MA</searchLink>; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Ahrens-Nicklas+RC%22">Ahrens-Nicklas RC</searchLink>; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Division of Human Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Li+Q%22">Li Q</searchLink>; Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA.; PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA.<br /><searchLink fieldCode="AU" term="%22Musunuru+K%22">Musunuru K</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. kiranmusunuru@gmail.com.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. kiranmusunuru@gmail.com.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. kiranmusunuru@gmail.com.; Division of Human Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA, USA. kiranmusunuru@gmail.com.<br /><searchLink fieldCode="AU" term="%22Alameh+MG%22">Alameh MG</searchLink>; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. mg.alameh@pennmedicine.upenn.edu.; Department of Bioengineering, George Mason University, Fairfax, VA, USA. mg.alameh@pennmedicine.upenn.edu.; Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mg.alameh@pennmedicine.upenn.edu.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. mg.alameh@pennmedicine.upenn.edu.<br /><searchLink fieldCode="AU" term="%22Peranteau+WH%22">Peranteau WH</searchLink>; The Center for Fetal Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA. peranteauw@chop.edu.; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA. peranteauw@chop.edu.<br /><searchLink fieldCode="AU" term="%22Wang+X%22">Wang X</searchLink>; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. xiao8@pennmedicine.upenn.edu.; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. xiao8@pennmedicine.upenn.edu.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. xiao8@pennmedicine.upenn.edu.
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