linical Efficacy and Bioethical Challenges of CRISPR–Cas9 Technology in the Treatment of Monogenic Genetic Disorders

Abstract

Monogenic genetic disorders are caused primarily by pathogenic variants affecting a single gene and represent an important group of inherited diseases. Although many of these conditions are individually rare, their cumulative impact on global health is substantial. Conventional treatment strategies are often directed toward controlling symptoms and reducing complications rather than correcting the underlying genetic defect. Recent advances in genome-editing technologies, particularly the CRISPR–Cas9 system, have created new opportunities for targeted treatment at the molecular level. This review aims to describe the biological basis and therapeutic potential of CRISPR–Cas9 technology in monogenic genetic disorders, with particular attention to its clinical applications, therapeutic efficacy, limitations, safety concerns, and associated bioethical challenges. A narrative review was performed using information presented in the available scientific literature and reference sources cited in the original article, including the World Health Organization, NCBI GeneReviews, Orphanet, ClinicalTrials.gov, the U.S. Food and Drug Administration, The New England Journal of Medicine, npj Genomic Medicine, and relevant biotechnology and pharmaceutical sources. The review focuses on monogenic disorders for which CRISPR-based therapeutic approaches have been investigated or clinically evaluated. CRISPR–Cas9 enables targeted modification of DNA through a guide RNA and the Cas9 endonuclease. The technology has been investigated in several monogenic disorders, including sickle cell disease, β-thalassemia, hereditary transthyretin amyloidosis, hereditary angioedema, inherited retinal disorders, and other genetic conditions. Clinical development of CRISPR-based therapies has demonstrated the potential to modify disease-associated genetic mechanisms rather than merely alleviate symptoms. Casgevy (exagamglogene autotemcel), based on CRISPR-mediated genome editing, represents an important clinical milestone in the development of gene-editing therapy for sickle cell disease and transfusion-dependent β-thalassemia. CRISPR–Cas9 and its newer derivatives represent promising approaches for the treatment of monogenic genetic disorders. Nevertheless, challenges related to off-target effects, long-term safety, delivery, accessibility, cost, and the ethical implications of germline genome editing remain important. Continued clinical research, long-term monitoring, and appropriate ethical and regulatory oversight are essential for the responsible development of genome editing therapies