Efficient Genome Editing in the Mouse Brain by Local Delivery of Engineered Cas9 Ribonucleoprotein Complexes

Nat Biotechnol. 2017 May;35(5):431-434. doi: 10.1038/nbt.3806. Epub 2017 Feb 13.

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.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Brain / physiology*
  • CRISPR-Associated Protein 9
  • CRISPR-Associated Proteins / administration & dosage
  • CRISPR-Associated Proteins / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • Endonucleases / genetics*
  • Gene Editing / methods*
  • Gene Targeting / methods
  • Male
  • Mice
  • Nerve Tissue Proteins / physiology*
  • Protein Engineering / methods
  • Ribonucleoproteins / genetics*

Substances

  • Bacterial Proteins
  • CRISPR-Associated Proteins
  • Nerve Tissue Proteins
  • Ribonucleoproteins
  • CRISPR-Associated Protein 9
  • Cas9 endonuclease Streptococcus pyogenes
  • Endonucleases