eng Rovedar Journal of Lab Animal Research 2980-9703 2025-12-29 4 6 67 77 10.58803/jlar.v4i6.91 101 Farshad Shahkhah 0 https://orcid.org/0009-0009-4689-3258 Mehran Bahmani 1 https://orcid.org/0009-0009-3478-6658 Diana Abbasi 2 https://orcid.org/0009-0004-6969-5143 Faezeh Sadat Moazzeni 3 https://orcid.org/0009-0006-5827-6183 Amin Shahinzadeh 4 https://orcid.org/0009-0008-3249-2878 Fatemeh Keikha 5 https://orcid.org/0009-0006-7265-3846 Marziyeh Saki 6 https://orcid.org/0009-0007-9897-9673 Department of Clinical Pathology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahvaz, Iran Department of Basic Science, Faculty ofNursing and Midwifery, Kurdistan University of Medical Science, Sanandaj, Iran Doctor of Veterinary Medicine Student, Department of Clinical Sciences, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran Doctor of Veterinary Medicine, Department of Clinical Sciences, Faculty of Veterinary Medicine, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran Doctor of Veterinary Medicine Student, Department of Clinical Sciences, Faculty of Veterinary Medicine, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran Doctor of Veterinary Medicine, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran The emergence of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome-editing technology represents fundamental changes with significant implications for oral and maxillofacial medicine. The present study aimed to synthesize current evidence from fundamental in vitro studies, engineered animal models, and emerging clinical trials to critically evaluate the potential applications and challenges of this biotechnology. The current review explored the transformative effects of CRISPR-Cas9 in key issues, including developing animal models for oral cancer and hereditary syndromes, ex vivo cell engineering for immunotherapies such as Chimeric antigen receptor (CAR) T-cell (CAR-T cells) for head and neck cancers, regenerative strategies using CRISPR-enhanced induced pluripotent stem cells (iPSCs) for salivary gland and enamel repair, and rapid diagnostic platforms for oral pathogens. Although preclinical data from murine models and organoid systems offered considerable potential for target validation and mechanistic understanding, their adoption in clinical settings is constrained by significant limitations. These limitations included the lack of tissue-specific delivery vectors, including standard lipid nanoparticles or viral vectors, unresolved off-target effects, long-term safety concerns, and complex ethical and regulatory challenges. The most immediate clinical impact was anticipated in two key areas, including CRISPR-based diagnostic tools such as the SHERLOCK platform, used for identifying SARS-CoV-2 variants or drug-resistant tuberculosis, and ex vivo cellular therapies being tested in controlled trials for specific diseases. The current findings indicated that integrating CRISPR into personalized oral healthcare required coordinated efforts to overcome translational barriers, conduct thorough clinical validation, and develop standardized safety and efficacy criterion specific to dental and maxillofacial outcomes. https://jlar.rovedar.com/index.php/JLAR/article/view/91 Animal model CRISPR/Cas9 Gene editing Oral disease Maxillofacial medicine