CRISPR-Cas Systems in Targeted Gene Therapy: Advances, Challenges, and Clinical Applications

Review Article

Abstract

CRISPR-Cas systems have emerged as a revolutionary genome-editing platform, enabling precise and efficient modifications of DNA sequences in living organisms. The simplicity, versatility, and programmability of CRISPR-Cas, particularly the Cas9 endonuclease, have accelerated research in targeted gene therapy for inherited disorders, cancer, and viral infections. This review highlights recent advancements in CRISPR-based therapeutic strategies, including ex vivo and in vivo genome editing, delivery mechanisms, and off-target minimization techniques. Key challenges such as immunogenicity, delivery efficiency, ethical considerations, and regulatory barriers are discussed. Clinical applications of CRISPR-Cas therapies in hemoglobinopathies, metabolic disorders, and cancer immunotherapy are evaluated, with emphasis on ongoing clinical trials and translational potential. Emerging technologies, including base editing, prime editing, and epigenetic modulation, further expand the therapeutic possibilities of CRISPR systems. Despite technical and ethical hurdles, CRISPR-Cas-mediated gene therapy holds transformative potential for personalized medicine, offering long-term cures for previously untreatable diseases.