ADVANCES, CLINICAL TRANSLATION AND EMERGING CHALLENGES IN GENE THERAPY: FROM VIRAL VECTOR ENGINEERING AND GENOME EDITING TO PRECISION AND PERSONALIZED GENETIC MEDICINE

The advent of genome editing technologies, most notably CRISPR-Cas systems, has further expanded the therapeutic scope of gene therapy by enabling precise modification of endogenous DNA. Genome editing allows direct correction of pathogenic mutations, targeted gene disruption, and modulation of gene expression, marking a conceptual shift from gene addition toward permanent genetic repair. The clinical approval of CRISPR-based therapies and the rapid translation of engineered T-cell therapies, such as chimeric antigen receptor T-cell therapy, illustrate the growing feasibility and impact of these approaches across oncology, hematology, and emerging non-malignant indications. Despite remarkable progress, significant barriers continue to limit broader implementation of gene therapy. Immunogenicity to viral vectors and transgene products, manufacturing complexity, scalability constraints, long-term safety monitoring requirements, and unprecedented treatment costs remain critical challenges. The economic burden associated with gene therapies necessitates innovative reimbursement models and policy frameworks to ensure sustainability and equitable access. Ethical considerations, including informed consent, long-term risk assessment, and governance of genome editing technologies, are increasingly central as gene therapy expands to more common and complex diseases. Gene therapy now represents a diverse and rapidly evolving ecosystem of therapeutic platforms rather than a single technological approach. Continued innovation in delivery systems, genome editing precision, manufacturing processes, and regulatory frameworks will be essential to fully realize it’s potential. As integration into routine clinical practice accelerates, multidisciplinary collaboration, rigorous long-term surveillance, and responsible ethical oversight will be critical to ensuring that gene therapy fulfills its promise as a cornerstone of precision and personalized medicine. Gene therapy has emerged as a transformative paradigm in modern biomedical science, fundamentally redefining approaches to disease treatment by targeting underlying genetic and molecular mechanisms rather than solely managing clinical symptoms. Over the past four decades, advances in molecular biology, virology, genome engineering, and translational medicine have driven the evolution of gene therapy from an experimental concept to a clinically validated therapeutic modality with multiple regulatory approvals and expanding indications. This comprehensive review critically examines the scientific foundations, technological breakthroughs, clinical achievements, and persistent challenges shaping the contemporary gene therapy landscape. The gene therapy now represents a diverse and rapidly evolving ecosystem of therapeutic platforms rather than a single technological approach. Continued innovation in delivery systems, genome editing precision, manufacturing processes, and regulatory frameworks will be essential to fully realize it’s potential. As integration into routine clinical practice accelerates, multidisciplinary collaboration, rigorous long-term surveillance, and responsible ethical oversight will be critical to ensuring that gene therapy fulfills its promise as a cornerstone of precision and personalized medicine.