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:: Volume 34, Issue 2 (5-2026) ::
Journal of Ilam University of Medical Sciences 2026, 34(2): 55-70 Back to browse issues page
Genome Editing Using the CRISPR–Cas9 System in Lynch Syndrome: From Molecular Insights to Clinical Perspectives
Elena Lak1 , Homayon Yousefi2 , Safa Radmehr *3
1- Alimentary Tract Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran , safa.radmehr1398@gmail.com
Abstract:   (484 Views)
Introduction:  Lynch Syndrome, caused by mutations in DNA mismatch repair genes, is the most common inherited cause of colorectal cancer. Despite advances in diagnosis, definitive targeted treatment remains challenging. CRISPR-Cas9 technology and its newer versions, such as base editing and prime editing, have provided new possibilities for precise genome editing. This study aimed to review the applications of these technologies and the challenges facing their clinical use in Lynch syndrome.
Materials & Methods: This narrative review was conducted by searching PubMed, Scopus, Google Scholar, and Web of Science databases between 2010 and 2026. Keywords related to Lynch syndrome, CRISPR-Cas9, microsatellite instability, and genome editing were used. Relevant original articles, systematic reviews, and case reports were included.
Results: Four main areas of application were identified: disease modelling, sensitive diagnosis of microsatellite instability and MMR mutations, direct correction of pathogenic variants in laboratory models, and design of personalised therapy using patient-derived organoids. Major challenges included off-target effects, inefficient delivery of CRISPR components to target tissues (especially colon and endometrium), high mutation diversity, and ethical issues related to germline editing.
Conclusion: CRISPR-Cas9 and its derivatives hold significant potential to transform diagnosis and treatment of Lynch syndrome, but a considerable gap remains before routine clinical application. Bridging this gap requires development of targeted delivery systems, use of high-fidelity Cas9 variants, and formulation of clear ethical and legal frameworks. Combining CRISPR with immunotherapy represents a promising future perspective.
 
Keywords: Lynch Syndrome, CRISPR-Cas9, Microsatellite Instability, Genome Editing, Personalized Medicine
Full-Text [PDF 1071 kb]   (211 Downloads)    
Editorial Note: Applicable | Subject: Molecular Genetics
Received: 2025/12/9 | Accepted: 2026/02/21 | Published: 2026/05/26
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Lak E, Yousefi H, Radmehr S. Genome Editing Using the CRISPR–Cas9 System in Lynch Syndrome: From Molecular Insights to Clinical Perspectives. J. Ilam Uni. Med. Sci. 2026; 34 (2) :55-70
URL: http://sjimu.medilam.ac.ir/article-1-8859-en.html
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مجله دانشگاه علوم پزشکی ایلام Journal of Ilam University of Medical Sciences
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