CRISPR-Cas9-Mediated Gene Editing in Hematological Disorders: Advancing Translational and Clinical Applications

Clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9)-mediated gene editing has emerged as a pivotal advancement in hematological medicine, addressing genetic and regulatory abnormalities underlying inherited and acquired blood disorders. Conventional therapeutic strategies offer symptomatic control or partial disease modification, leaving substantial unmet clinical need for durable, mechanism-driven interventions. This narrative review aims to synthesize the translational and clinical progress of CRISPR-Cas9 applications in hematological disorders, with an emphasis on therapeutic strategies, safety considerations, and integration into clinical practice. A comprehensive literature evaluation was conducted using major biomedical databases, selecting peer-reviewed studies published between 2015 and 2025 that reported mechanistic, translational, or clinical relevance in hematology. Eligible literature included experimental investigations, clinical trials, and high-quality reviews, with exclusion of non-translational and germline-focused studies. This review highlights advances in hematopoietic stem cell editing, correction of hemoglobinopathies, immune cell engineering, and chimeric antigen receptor-based therapies, as well as progress in delivery platforms and high-fidelity nuclease designs. Key challenges related to off-target effects, genomic stability, manufacturing scalability, regulatory oversight, and ethical governance are critically evaluated. Emerging clinical trial outcomes demonstrate sustained therapeutic benefit and expanding feasibility across diverse hematological indications. Long-term clinical monitoring remains central to evaluating durability and safety. Collectively, current evidence supports CRISPR-Cas9 as a cornerstone technology in precision hematology, with continued optimization required to enable safe, equitable, and widespread clinical adoption.