Current Drug Targets · Oct 21, 2026

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

By Fatima J, Siddique YH

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.

doi.org/10.2174/0113894501509343261013070100PubMed 42973349Interventions