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Updated: Feb 6, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice
Dan Wang1,2,3, Jia Li1,2, Chun-Qing Song4
1Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
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.
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