Precision Genome Engineering in Human Disease: Expanding Therapeutic Roles of CRISPR Technologies.

Abstract

The advent of CRISPR-Cas9 technology has revolutionized genome editing, enabling precise modifications to the human genome with unprecedented accuracy and sequence specificity. This review examines current mechanistic insights, translational advances, and clinical developments in gene editing, focusing on applications in diabetes mellitus, cancer, hematologic disorders, neurodegenerative diseases, and autoimmune pathologies. This study provides a comprehensive analysis of recent literature on CRISPR-based genome editing, emphasizing next-generation modalities like base editing and prime editing, and their impact on target specificity and genomic integrity. Therapeutic strategies involving ex vivo editing of hematopoietic stem cells and in vivo delivery approaches, including lipid nanoparticle-mediated systems, are evaluated. Base editing and prime editing have improved sequence specificity and reduced double-strand DNA breaks, enhancing safety profiles. Ex vivo editing of hematopoietic stem cells for hemoglobinopathies and in vivo genome editing via lipid nanoparticles show translational promise. However, limitations persist: off-target effects, immunogenicity, delivery inefficiencies, and ethical concerns surrounding germline editing require careful consideration. Gene editing technologies show potential for treating previously intractable diseases. Technical, safety, and ethical challenges must be addressed through continued refinement of editing platforms, rigorous scientific validation, and the establishment of robust governance frameworks to ensure safe and responsible translation into clinical medicine.