ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
CRISPR/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I.
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 27 citations in OpenAlex.
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- CRISPR/Cas9 in perspective: evaluating efficacy, delivery methods, and ethical challenges in genome editing.Molecular biology reports · 2026Review
- Animal models of chronic thromboembolic pulmonary hypertension.Animal models and experimental medicine · 2026Review
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- Efficient AAV8 delivery to the liver via isolated hepatic perfusion and analysis of hepatic lobule transduction patterns.Liver research (Beijing, China) · 2025Article
- Progress in Gene Therapy for Hereditary Tyrosinemia Type 1.Pharmaceutics · 2025Review
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- In vivo evaluation of guide-free Cas9-induced safety risks in a pig model.Signal transduction and targeted therapy · 2024Article
- Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.Hepatology communications · 2024Article
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Construction and functional verification of size-reduced plasmids based on TMP resistance geneMicrobiology spectrum · 2023Article
- Activation of homology-directed DNA repair plays key role in CRISPR-mediated genome correction.Gene therapy · 2023Article
- mRNA and gene editing: Late breaking therapies in liver diseases.Hepatology (Baltimore, Md.) · 2022Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.Cellular & molecular biology letters · 2022Review
- Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics.Precision clinical medicine · 2021Review
- Genetically blockingMolecular therapy. Methods & clinical development · 2021Article
- Role of Noncoding RNAs in Acetaminophen-Induced Liver Injury.Gene expression · 2021Review
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Authors and funding
21 authors at 5 institutions in 1 country.
Nan LiCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Shixue GouCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Jiaowei WangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Quanjun ZhangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
Xingyun HuangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Jingke XieCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Li LiCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.
Qin JinCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Zhen OuyangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
Fangbing ChenCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Weikai GeCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Hui ShiCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Yanhui LiangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Zhenpeng ZhuangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Xiaozhu ZhaoCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Meng LianCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Institute of Physical Science and Information Technology, Anhui University, Hefei 230601, China.
Yinghua YeCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
Longquan QuanCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
Han WuCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China. Electronic address: wu_han@gibh.ac.cn.
Liangxue LaiCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China. Electronic address: lai_liangxue@gibh.ac.cn.
Kepin WangCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China. Electronic address: wang_kepin@gibh.ac.cn.
Guangzhou Medical University · CNGuangzhou Institutes of Biomedicine and Health · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNGuangzhou Regenerative Medicine and Health Guangdong Laboratory · CNUniversity of Chinese Academy of Sciences · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 offspring. Adeno-associated virus (AAV)-treated HT1 rabbits displayed normal liver and kidney structures and functions. Homology-directed repair-mediated precise gene corrections and non-homologous end joining-mediated out-of-frame to in-frame corrections in the livers were observed with efficiencies of 0.90%-3.71% and 2.39%-6.35%, respectively, which appeared to be sufficient to recover liver function and decrease liver and kidney damage. This study provides useful large-animal preclinical data for rescuing hepatocyte-related monogenetic metabolic disorders with precise gene therapy.
Indexed as
CRISPR-Cas SystemsGene EditingAnimalsAnimals, NewbornDependovirusDisease Models, AnimalDNA End-Joining RepairFemaleGene Expression RegulationGenetic TherapyGenetic VectorsHydrolasesKidneyLiverMaleRabbitsfumarylacetoacetaseHydrolasesadeno-associated virusCRISPR-Cas9-mediated precise gene therapyhereditary tyrosinemia type Irabbit models
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