_1770265366 20260205042246000 Rovedar Daryoushbabazadeh@gmail.com Rovedar Journal of Lab Animal Research J Lab Anim. Res 2980-9703 12 29 2025 4 6 Farshad Shahkhah https://orcid.org/0009-0009-4689-3258 Mehran Bahmani https://orcid.org/0009-0009-3478-6658 Diana Abbasi https://orcid.org/0009-0004-6969-5143 Faezeh Sadat Moazzeni https://orcid.org/0009-0006-5827-6183 Amin Shahinzadeh https://orcid.org/0009-0008-3249-2878 Fatemeh Keikha https://orcid.org/0009-0006-7265-3846 Marziyeh Saki https://orcid.org/0009-0007-9897-9673 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. 12 29 2025 67 77 https://creativecommons.org/licenses/by/4.0 10.58803/jlar.v4i6.91 https://jlar.rovedar.com/index.php/JLAR/article/view/91 https://jlar.rovedar.com/index.php/JLAR/article/download/91/122 https://jlar.rovedar.com/index.php/JLAR/article/download/91/122 10.1007/978-1-0716-4690-8_7 World health organization (WHO). 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