Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice

Nat Biotechnol. 2018 Oct;36(9):839-842. doi: 10.1038/nbt.4219. Epub 2018 Aug 13.


We report a genome-editing strategy to correct compound heterozygous mutations, a common genotype in patients with recessive genetic disorders. Adeno-associated viral vector delivery of Cas9 and guide RNA induces allelic exchange and rescues the disease phenotype in mouse models of hereditary tyrosinemia type I and mucopolysaccharidosis type I. This approach recombines non-mutated genetic information present in two heterozygous alleles into one functional allele without using donor DNA templates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • CRISPR-Associated Protein 9*
  • Dependovirus / genetics
  • Gene Editing
  • Genes, Recessive*
  • Genetic Vectors
  • Heterozygote*
  • Mice
  • Mutation*


  • CRISPR-Associated Protein 9