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, Dan; Li, Jia; Song, Chun-Qing; Tran, Karen; Mou, Haiwei; Pei-Hsuan Wu; Tai, Phillip W. L. L; Mendonca, Craig A.; Ren, Lingzhi; Wang, Blake Y.; Su, Qin; Gessler, Dominic J.; Zamore, Phillip D.; Xue, Wen; and Gao, Guangping, "Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice" (2018). RNA Therapeutics Institute Publications. 52.