CRISPR/Cas9-based Genome Editing in Inherited Diseases: Mechanisms, Therapeutic Advances, Safety and Clinical Translation

Abstract:

Gene therapy has transformed modern biomedical research by enabling curative strategies that target the molecular basis of disease. Among genome-editing technologies, the CRISPR/Cas9 system has emerged as a versatile and efficient platform due to its programmability, simplicity, and precision. This review summarizes the evolution of gene therapy and highlights the therapeutic potential of CRISPR-based genome editing. CRISPR/Cas9 has demonstrated significant potential in correcting disease-causing mutations across multiple inherited disorders, including sickle cell disease, β- thalassemia, familial hypercholesterolemia, phenylketonuria, muscular dystrophies, and cystic fibrosis. Emerging technologies such as base editing and prime editing further improved editing precision and reduced unintended genomic alterations. However, challenges including off-target effects, DNA repair pathway bias, immune responses, and vector-associated toxicities remain major limitations. The review highlights the rapid progress of CRISPR-mediated therapeutics and emphasizes the importance of improving editing accuracy, delivery efficiency, and long-term safety. Advances in vector engineering and genome-editing platforms are expected to overcome current technical and ethical barriers, facilitating broader clinical applications. CRISPR/Cas9 and related genome- editing technologies represent promising disease-modifying and potentially curative therapeutic approaches. Continued optimization of precision, safety, and delivery systems will be essential for successful translation into routine clinical practice.