biostudies-literatureUnknown29(3)Li NScience and Technology Planning Project of Guangdong ProvinceGuangzhou Municipal Science and Technology ProjectChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaYouth Innovation Promotion Association of the Chinese Academy of SciencesPatients with hereditary tyrosinemia type I (HT1) present acute and irreversible liver and kidney damage during infancy. CRISPR-Cas9-mediated gene correction during infancy may provide a promising approach to treat patients with HT1. However, all previous studies were performed on adult HT1 rodent models, which cannot authentically recapitulate some symptoms of human patients. The efficacy and safety should be verified in large animals to translate precise gene therapy to clinical practice. Here, we delivered CRISPR-Cas9 and donor templates via adeno-associated virus to newborn HT1 rabbits. The lethal phenotypes could be rescued, and notably, these HT1 rabbits reached adulthood normally without 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione administration and even gave birth to Molecular therapy : the journal of the American Society of Gene Therapy1001-1015https://www.ebi.ac.uk/biostudies/studies/S-EPMC7934638biostudies-literatureCRISPR/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I.PMC7934638Jin QLiang YChen FQuan LYe YWang JLi LZhang QZhuang ZWang KLi NZhao XWu HLian MGe WHuang XXie JOuyang ZGou SLai LShi HfalseCRISPR/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I.Patients with hereditary tyrosinemia type I (HT1) present acute and irreversible liver and kidney damage during infancy. CRISPR-Cas9-mediated gene correction during infancy may provide a promising approach to treat patients with HT1. However, all previous studies were performed on adult HT1 rodent models, which cannot authentically recapitulate some symptoms of human patients. The efficacy and safety should be verified in large animals to translate precise gene therapy to clinical practice. Here, we delivered CRISPR-Cas9 and donor templates via adeno-associated virus to newborn HT1 rabbits. The lethal phenotypes could be rescued, and notably, these HT1 rabbits reached adulthood normally without 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione administration and even gave birth to 2021-01-01T00:00:00Z2021 Mar2026-05-02T11:23:22.711Z2025-02-19T03:26:52.226ZS-EPMC79346383322143410.1016/j.ymthe.2020.11.023