ArticleSignal transduction and targeted therapy2021
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 23 citations in OpenAlex.
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- Preclinical models in the study of lymph node metastasis.Journal of Zhejiang University. Science. B · 2025Review
- An Anti-CD147 Antibody-Drug Conjugate Mehozumab-DM1 is Efficacious Against Hepatocellular Carcinoma in Cynomolgus Monkey.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Unexpected mutations occurred in CRISPR/Cas9 edited Drosophila analyzed by deeply whole genomic sequencing.Heliyon · 2024Article
- Precision Oncology in Pancreatic Cancer: Experiences and Challenges of the CCCMunichTargeted oncology · 2023Article
- Genome editing in cancer: Challenges and potential opportunities.Bioactive materials · 2023Article
- Emerging Nano-/Biotechnology Drives Oncolytic Virus-Activated and Combined Cancer Immunotherapy.Research (Washington, D.C.) · 2023Article
- Gene editing monkeys: Retrospect and outlook.Frontiers in cell and developmental biology · 2022Review
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20 authors at 2 institutions in 2 countries.
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Abstract
Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.
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