Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice
Horae Gene Therapy Center; Li Weibo Institute for Rare Diseases Research; Department of Microbiology and Physiological Systems; RNA Therapeutics Institute; Viral Vector Core; Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetic Phenomena | Genetics and Genomics
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.
DOI of Published Version
Nat Biotechnol. 2018 Oct;36(9):839-842. doi: 10.1038/nbt.4219. Epub 2018 Aug 13. Link to article on publisher's site
Wang D, Li J, Song C, Tran K, Mou H, P, Tai PW, Mendonca CA, Ren L, Wang BY, Su Q, Gessler DJ, Zamore PD, Xue W, Gao G. (2018). Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice. RNA Therapeutics Institute Publications. https://doi.org/10.1038/nbt.4219. Retrieved from https://escholarship.umassmed.edu/rti_pubs/52