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Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.
Stahl, Elizabeth C; Sabo, Jennifer K; Kang, Min Hyung; Allen, Ryan; Applegate, Elizabeth; Kim, Shin Eui; Kwon, Yoonjin; Seth, Anmol; Lemus, Nicholas; Salinas-Rios, Viviana; Soczek, Katarzyna M; Trinidad, Marena; Vo, Linda T; Jeans, Chris; Wozniak, Anna; Morris, Timothy; Kimberlin, Athen; Foti, Thomas; Savage, David F; Doudna, Jennifer A.
Affiliation
  • Stahl EC; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA
  • Sabo JK; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Kang MH; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Allen R; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Applegate E; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Kim SE; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Kwon Y; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Seth A; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Lemus N; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Salinas-Rios V; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Soczek KM; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA
  • Trinidad M; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Vo LT; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Jeans C; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
  • Wozniak A; Aldevron LLC, Madison, WI 53719, USA.
  • Morris T; Aldevron LLC, Madison, WI 53719, USA.
  • Kimberlin A; Aldevron LLC, Madison, WI 53719, USA.
  • Foti T; Aldevron LLC, Madison, WI 53719, USA.
  • Savage DF; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Doudna JA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA
Mol Ther ; 31(8): 2422-2438, 2023 08 02.
Article in En | MEDLINE | ID: mdl-37403358
ABSTRACT
Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CRISPR-Cas Systems / Gene Editing Limits: Animals Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2023 Type: Article Affiliation country: Canada
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CRISPR-Cas Systems / Gene Editing Limits: Animals Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2023 Type: Article Affiliation country: Canada