Scientific article
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English

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

Published inNature biotechnology, vol. 36, no. 9, p. 839-842
Publication date2018-10
First online date2018-08-13
Abstract

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.

Keywords
  • Alleles
  • Animals
  • CRISPR-Associated Protein 9
  • Dependovirus / genetics
  • Gene Editing
  • Genes, Recessive
  • Genetic Vectors
  • Heterozygote
  • Mice
  • Mutation
Affiliation entities Not a UNIGE publication
Funding
  • NHLBI NIH HHS - [P01 HL131471]
  • NIAID NIH HHS - [R01 AI121135]
  • NIAID NIH HHS - [P01 AI100263]
  • NICHD NIH HHS - [P01 HD080642]
  • NINDS NIH HHS - [R01 NS076991]
  • NHLBI NIH HHS - [UG3 HL147367]
  • NHLBI NIH HHS - [DP2 HL137167]
Citation (ISO format)
WANG, Dan et al. Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice. In: Nature biotechnology, 2018, vol. 36, n° 9, p. 839–842. doi: 10.1038/nbt.4219
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Identifiers
Journal ISSN1087-0156
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83downloads

Technical informations

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