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

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.

SUBMITTER: Wang D

PROVIDER: S-EPMC6126964 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Wang Dan D Li Jia J Song Chun-Qing CQ Tran Karen K Mou Haiwei H Wu Pei-Hsuan PH Tai Phillip W L PWL Mendonca Craig A CA Ren Lingzhi L Wang Blake Y BY Su Qin Q Gessler Dominic J DJ Zamore Phillip D PD Xue Wen W Gao Guangping G

Nature biotechnology 20180813 9

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 ...[more]

PMID: 30102296

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