Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons

Hereditary hematological disorders, including sickle cell disease, β-thalassemia, and hemophilia, are severe monogenic diseases that impose substantial morbidity and lifelong treatment burdens. Conventional therapies are largely supportive and rarely curative, whereas gene therapy is increasingly transforming the therapeutic landscape by addressing the underlying genetic defects. This review summarizes the major gene therapy strategies currently being developed for hereditary hematological disorders, with a particular focus on gene addition, gene editing, and gene silencing, as well as ex vivo and in vivo delivery platforms. We highlight recent clinical breakthroughs, including approved products for hemoglobinopathies and hemophilia, and discuss emerging approaches such as base editing, prime editing, epigenetic modulation, and lipid nanoparticle-mediated delivery. In addition, we examine the major challenges that continue to limit broader clinical adoption, including immune responses, off-target effects, conditioning-related toxicity, manufacturing complexity, high cost, and limited accessibility. Finally, we outline future directions that may accelerate clinical translation, including improved editing precision, next-generation vector engineering, artificial intelligence-assisted design, scalable manufacturing, and more equitable access to treatment. Together, these advances suggest that gene therapy is steadily moving from experimental innovation toward durable, potentially curative treatment for hereditary hematological disorders.