CRISPR-CAS9 AND BASE EDITING: RECENT CLINICAL PROGRESS AND DELIVERY CHALLENGES IN GENE THERAPY

CRISPR-Cas9 genome editing has progressed rapidly from laboratory tool to clinical intervention, offering the possibility of durable correction of genetic diseases. Ex vivo editing of hematopoietic stem cells has produced promising results in sickle cell disease and β-thalassemia, while in vivo editing of the transthyretin gene has demonstrated the feasibility of systemic delivery using lipid nanoparticles. Base editing, which enables precise single-nucleotide conversions without introducing double-strand breaks, has emerged as a complementary approach with potential advantages in safety and precision. This review examines recent clinical progress in CRISPR-Cas9 and base editing therapies through early 2023, with a focus on the underlying mechanisms, key clinical data, and persistent delivery challenges. Ex vivo applications are contrasted with in vivo strategies, and the limitations of adeno-associated virus vectors, lipid nanoparticles, and other delivery systems are critically discussed. Off-target editing, immunogenicity, and the need for long-term safety data remain central concerns. Future directions include improved delivery vehicles, prime editing, and multiplexed correction strategies. The evidence indicates that CRISPR-based therapies are entering a decisive phase, but substantial technical and regulatory hurdles must be addressed before broad clinical application.