Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.

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Title: Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.
Authors: Giddins M; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA., Kratz AF; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA., De Los Santos MB; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Neurobiology and Behavior Program, Columbia University Irving Medical Center, New York, NY, USA.; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA., Forget A; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA., Tiwari R; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA., Jang G; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA., Blazejewski T; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA., Qin C; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK.; The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, UK., Huang Y; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA., Lao YH; Department of Biomedical Engineering, Columbia University, New York, NY, USA.; Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA., Falconer T; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA., Leong KW; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Krogan N; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.; Gladstone Institutes, San Francisco, CA, USA., Staller M; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.; Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA.; Chan Zuckerberg Biohub-San Francisco, San Francisco, CA, USA., Wang H; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA., Wei L; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA. larrywei@health.ucsd.edu.; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. larrywei@health.ucsd.edu., Chavez A; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA. chavez2@health.ucsd.edu.; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. chavez2@health.ucsd.edu.
Source: Nature communications [Nat Commun] 2025 Nov 20; Vol. 16 (1), pp. 11114. Date of Electronic Publication: 2025 Nov 20.
Publication Type: Journal Article
Journal Info: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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  Data: <searchLink fieldCode="AU" term="%22Giddins+M%22">Giddins M</searchLink>; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Kratz+AF%22">Kratz AF</searchLink>; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22De+Los+Santos+MB%22">De Los Santos MB</searchLink>; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Neurobiology and Behavior Program, Columbia University Irving Medical Center, New York, NY, USA.; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Forget+A%22">Forget A</searchLink>; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.<br /><searchLink fieldCode="AU" term="%22Tiwari+R%22">Tiwari R</searchLink>; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.<br /><searchLink fieldCode="AU" term="%22Jang+G%22">Jang G</searchLink>; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.<br /><searchLink fieldCode="AU" term="%22Blazejewski+T%22">Blazejewski T</searchLink>; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Qin+C%22">Qin C</searchLink>; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK.; The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, UK.<br /><searchLink fieldCode="AU" term="%22Huang+Y%22">Huang Y</searchLink>; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Lao+YH%22">Lao YH</searchLink>; Department of Biomedical Engineering, Columbia University, New York, NY, USA.; Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.<br /><searchLink fieldCode="AU" term="%22Falconer+T%22">Falconer T</searchLink>; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Leong+KW%22">Leong KW</searchLink>; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Krogan+N%22">Krogan N</searchLink>; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.; Gladstone Institutes, San Francisco, CA, USA.<br /><searchLink fieldCode="AU" term="%22Staller+M%22">Staller M</searchLink>; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.; Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA.; Chan Zuckerberg Biohub-San Francisco, San Francisco, CA, USA.<br /><searchLink fieldCode="AU" term="%22Wang+H%22">Wang H</searchLink>; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Wei+L%22">Wei L</searchLink>; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA. larrywei@health.ucsd.edu.; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. larrywei@health.ucsd.edu.<br /><searchLink fieldCode="AU" term="%22Chavez+A%22">Chavez A</searchLink>; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA. chavez2@health.ucsd.edu.; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. chavez2@health.ucsd.edu.
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