title: Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes.
abstract: We demonstrate editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein (RNP) complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. These advances indicate the potential of genome editing in the brain to correct or inactivate the underlying genetic causes of neurological diseases.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Staahl
authors.affiliation: Roche Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Madhurima
authors.initials: M
authors.lastname: Benekareddy
authors.affiliation: Roche Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Claire
authors.initials: C
authors.lastname: Coulon-Bainier
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Banfal
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Floor
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Sabo
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
authors.forename: Cole
authors.initials: C
authors.lastname: Urnes
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
authors.forename: Gabriela Acevedo
authors.initials: GA
authors.lastname: Munares
authors.affiliation: Roche Pharma Research and Early Development, Basel, Switzerland.|E-Scape Bio, San Francisco, California, USA.
authors.forename: Anirvan
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.|Howard Hughes Medical Institute, University of California, Berkeley, California, USA.|Innovative Genomics Institute, University of California, Berkeley, California, USA.|MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.|Department of Chemistry, University of California, Berkeley, California, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doudna
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D000076987:CRISPR-Associated Protein 9; D064130:CRISPR-Associated Proteins / Q000008:administration & dosage / Q000235:genetics*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D004720:Endonucleases / Q000235:genetics*; D000072669:Gene Editing / Q000379:methods*; D018390:Gene Targeting / Q000379:methods; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D015202:Protein Engineering / Q000379:methods; D012261:Ribonucleoproteins / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D064130:CRISPR-Associated Proteins; D009419:Nerve Tissue Proteins; D012261:Ribonucleoproteins; D000076987:CRISPR-Associated Protein 9; C000606107:Cas9 endonuclease Streptococcus pyogenes; D004720:Endonucleases