CRISPR–Cas9: A comprehensive review of gene editing for inherited blood disorders

Abstract

The CRISPR–Cas9 system is a highly promising and versatile platform for genome editing with significant potential for gene therapy. It employs locus-specific nucleases, guided by programmable RNAs, to cleave target DNA sites and introduce double-strand breaks, thereby enabling precise genome modification through endogenous DNA repair mechanisms. This review aims to elucidate the relationship between CRISPR–Cas9 technology and inherited blood disorders, and to highlight the most important evidence-based recommendations for the diagnosis and effective management of these conditions. The review synthesises recent literature—including clinical trials, systematic reviews, and meta-analyses published between 2019 and 2022—identified through comprehensive searches of Web of Science, PubMed, PMC, ScienceDirect, Frontiers in Genome Editing, OJRD, AMJ Med, and Google Books using terms such as CRISPR–Cas9 system and inherited blood disorders. Studies involving gene modification of haematopoietic cells form the foundation for discussing contemporary models of blood diseases. We also summarise the applications of gene modification in experimental, preclinical, and clinical haematology, including gene-function interference, target identification, drug discovery, and chimeric antigen receptor or T-cell receptor engineering. Future research should prioritise the optimisation of delivery systems, improvement of target specificity, and evaluation of long-term safety. We hope that this review will support haematology practitioners and genetic research specialists in deepening their understanding of the impact of CRISPR–Cas9 on human biology and promote greater awareness across the healthcare system. Finally, we discuss the rapidly evolving landscape of haematology and the ongoing advancements in CRISPR–Cas9 technology that are poised to further transform the field.